Pain is a common symptom in stage IV non-small cell lung cancer (NSCLC). The objective of the study was to examine the use of interventions and factors associated with interventions for pain. A ...population-based cohort study in Ontario, Canada was conducted with patients diagnosed with stage IV NSCLC from January 2007 to September 2018. An Edmonton Symptom Assessment System (ESAS) score of ≥4 defined moderate-to-severe pain following diagnosis. The study cohort included 13,159 patients, of which 68.5% reported at least one moderate-to-severe pain score. Most patients were assessed by a palliative care team (85.4%), and the majority received radiation therapy (73.2%). The use of nerve block was rare (0.8%). For patients ≥65 years of age who had drug coverage, 59.6% received an opiate prescription. Patients with moderate-to-severe pain were more likely to receive palliative assessment or radiation therapy compared to patients with none or mild pain. Patients aged ≥70 years and with a greater comorbidity burden were associated with less likelihood to receive radiation therapy. Patients from rural/non-major urban residence and with a greater comorbidity burden were also less likely to receive palliative care assessment. Factors associated with interventions for pain are described to inform future symptom management in this population.
Background The purpose of this study was to use the Trial Outcome Index (TOI) to longitudinally assess the effects of treatment for esophageal cancer. Methods Patients with esophageal cancer treated ...with curative intent therapy (N = 84) were evaluated with Functional Assessment of Cancer Therapy—Esophageal Cancer subscale (FACT-E) questionnaires, which were scheduled at baseline and at 1, 3, 6, 9, 12, 18, 24, and 36 months after completion of treatment. Patients treated with preoperative therapy also completed questionnaires 6 to 8 weeks after starting treatment and after completion of induction treatment (12–14 weeks) just before the operative procedure. Physical and functional well-being subscales and the esophageal specific concerns that comprise the TOI were used for the analysis. A linear mixed-effects model with identity link function was used for longitudinal TOI scores. Tukey-Kramer adjustment for multiple comparisons was used for pairwise comparisons. Results TOI scores differed over time ( p < 0.0001), with a significant decrease in TOI from baseline to 6 to 8 weeks after chemotherapy or chemoradiation ( p < 0.0001; median, 95 versus 68). At 1 month after treatment (esophagectomy or definitive chemoradiation), median TOI scores were 79 ( p = 0.0011 compared with baseline). However by 3 months after treatment, median scores were 90, not significantly different from baseline ( p = 0.23). Beyond 3 months, TOI scores either increased or stabilized. Single patients have TOI scores 12 points lower than patients with partners ( p = 0.0015). Conclusions TOI is a useful tool to assess the physical and functional effects of treatment in patients with esophageal cancer and may provide an efficient index for the comparison of different types of treatment, particularly in the context of clinical trials.
Background Metabolomics is a potential means for biofluid-based lung cancer detection. We conducted a non-targeted, data-driven assessment of plasma from early-stage non-small cell lung cancer ...(ES-NSCLC) cases versus cancer-free controls (CFC) to explore and identify the classes of metabolites for further targeted metabolomics biomarker development. Methods Plasma from 250 ES-NSCLC cases and 250 CFCs underwent ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) in positive and negative electrospray ionization (ESI) modes. Molecular feature extraction, formula generation, and find-by-ion tools annotated metabolic entities. Analysis was restricted to endogenous metabolites present in greater than or equal to 80% of samples. Unsupervised hierarchical cluster analysis identified clusters of metabolites. The metabolites with the strongest correlation with the principal component of each cluster were included in logistic regression modeling to assess discriminatory performance with and without adjustment for clinical covariates. Results A total of 1900 UHPLC-QTOF-MS assessments identified 1667 and 2032 endogenous metabolites in the ESI-positive and ESI-negative modes, respectively. After data filtration, 676 metabolites remained, and 12 clusters of metabolites were identified from each ESI mode. Multivariable logistic regression using the representative metabolite from each cluster revealed effective classification of cases from controls with overall diagnostic accuracy of 91% (ESI positive) and 94% (ESI negative). Metabolites of interest identified for further targeted analysis include the following: 1b, 3a, 12a-trihydroxy-5b-cholanoic acid, pyridoxamine 5'-phosphate, sphinganine 1-phosphate, gamma-CEHC, 20-carboxy-leukotriene B4, isodesmosine, and 18-hydroxycortisol. Conclusions Plasma-based metabolomic detection of early-stage NSCLC appears feasible. Further metabolomics studies targeting phospholipid, steroid, and fatty acid metabolism are warranted to further develop noninvasive metabolomics-based detection of early-stage NSCLC. Keywords: Early-stage non-small cell lung cancer, Plasma metabolomics, Early detection, Non-targeted metabolomics
Objective Loss to follow-up (LTFU) can be a major difficulty for any clinical research study. The objective of this systematic review was to assess the extent of LTFU and its potential effect in ...studies of adult trauma patients with blunt thoracic aortic injuries (BTAIs). Methods Studies comparing management of BTAIs were systematically reviewed. Duplicate independent review was used for study selection, data abstraction, and critical appraisals. Results Thirty-six studies were included for synthesis, of which 94.1% applied a retrospective cohort design to prospective institutional databases. The mean LTFU at 1 year was 26.5% ± 31.6% for endovascular repair and 20.6% ± 34.2% for open repair groups. Not having a surgical/interventional specialist as a first or senior author was associated with a 39.7% higher LTFU at 1 year ( P = .002). Studies with a higher risk of bias, later publication year, or North American origin were associated with a significantly higher risk for LTFU at 1 year ( P ≤ .001). Nearly half of included studies assessed in-hospital outcomes exclusively. Only 38.2% explicitly reported LTFU data. Eight studies explicitly described the method of dealing with LTFU: eight used survival analysis and one used a national Social Security Death Index. Sensitivity analyses using plausible worst-case LTFU scenarios resulted in 14% to 17% of studies changing direction of effect. Conclusions There is significant LTFU in trauma studies comparing operative methods for BTAIs. LTFU is generally handled and reported suboptimally, and sensitivity analyses suggest that study results are sensitive to differential LTFU. This has implications for the evidence-based choice of the operative method. Some protective factors that may aid in reducing LTFU were identified, one of which was involvement of a surgical or interventional specialist as a key author.
ObjectiveAccurate estimates of survival guide decision-making for patients and oncologists. Advances in the capacity to measure complex tumour biology and patient factors allow for concurrent ...consideration of clinical, pathological, molecular, and biological markers for prognostication. Clinical prediction tools are a mechanism to combine and personalize these increasingly large amounts of complex information for prognostication.
ApproachWe describe the process of linking routinely collected health data, cancer registry, and pathology report data in two provinces to develop (Ontario, Canada) and validate (Manitoba, Canada) a clinical prediction tool in esophageal cancer. We compared the performance of a base model restricted to patient and disease characteristics available prior to surgical resection (e.g., age, sex, histology, comorbidities), and a more complex model including pathology specimen details (e.g., tumour stage). Cox proportional hazards models were fit to predict death at three years following resection. Internal and external validity was assessed using overall calibration and optimism corrected c-statistics. Equity was assessed through calibration in predefined patient subgroups.
Results2124 patients who underwent surgical resection for esophageal cancer between May 1, 2004 and June 30, 2016 for whom a pathology record was available were included in the study cohort. Median age was 66, with 80% males and 85% adenocarcinomas. Survival data were available until March 31, 2020. The model with pathology data had superior discrimination and calibration (calibration slope of 1.02 and intercept -0.01, and optimism-corrected c-statistic 0.77), compared to the base model (calibration slope of 0.95, intercept 0.02, and c-statistic 0.60). External validation is ongoing.
ConclusionOur study demonstrates that prediction models for cancer prognosis built solely on data from health administrative databases may be unreliable. The addition of high-quality pathology report data from electronic medical records or population-based cancer registries is necessary for accurate estimation. Our work provides a framework for combining administrative and clinical data which could be applied to the development of other clinical prediction models.
Endobronchial electromagnetic transponder beacons (EMT) provide real-time, precise positional data of moving lung tumors. We report results of a phase 1/2, prospective, single-arm cohort study ...evaluating the treatment planning effects of EMT-guided SABR for moving lung tumors.
Eligible patients were adults, Eastern Cooperative Oncology Group 0 to 2, with T1-T2N0 non-small cell lung cancer or pulmonary metastasis ≤4 cm with motion amplitude ≥5 mm. Three EMTs were endobronchially implanted using navigational bronchoscopy. Four-dimensional free-breathing computed tomography simulation scans were obtained, and end-exhalation phases were used to define the gating window internal target volume. A 3-mm expansion of gating window internal target volume defined the planning target volume (PTV). EMT-guided, respiratory-gated (RG) SABR was delivered (54 Gy/3 fractions or 48 Gy/4 fractions) using volumetric modulated arc therapy. For each RG-SABR plan, a 10-phase image-guided SABR plan was generated for dosimetric comparison. PTV/organ-at-risk (OAR) metrics were tabulated and analyzed using the Wilcoxon signed-rank pair test. Treatment outcomes were evaluated using RECIST (Response Evaluation Criteria in Solid Tumours; version 1.1).
Of 41 patients screened, 17 were enrolled and 2 withdrew from the study. Median age was 73 years, with 7 women. Sixty percent had T1/T2 non-small cell lung cancer and 40% had M1 disease. Median tumor diameter was 1.9 cm with 73% of targets located peripherally. Mean respiratory tumor motion was 1.25 cm (range, 0.53-4.04 cm). Thirteen tumors were treated with EMT-guided SABR and 47% of patients received 48 Gy in 4 fractions while 53% received 54 Gy in 3 fractions. RG-SABR yielded an average PTV reduction of 46.9% (P < .005). Lung V5, V10, V20, and mean lung dose had mean relative reductions of 11.3%, 20.3%, 31.1%, and 20.3%, respectively (P < .005). Dose to OARs was significantly reduced (P < .05) except for spinal cord. At 6 months, mean radiographic tumor volume reduction was 53.5% (P < .005).
EMT-guided RG-SABR significantly reduced PTVs of moving lung tumors compared with image-guided SABR. EMT-guided RG-SABR should be considered for tumors with large respiratory motion amplitudes or those located in close proximity to OARs.
AbstractBackgroundLung cancer is a major cause of global morbidity and mortality. Current low dose CT screening is invasive and its role remains contentious. There are no known biomarkers to monitor ...treatment response, detect disease recurrence and patient selection for adjuvant treatment after curative surgical resection. Hence there is an urgent need to explore non-conventional and noninvasive tools to develop novel biomarkers to improve the outcome of this lethal cancer. MethodsThis is an ongoing exploratory and translational study involving collection of bio fluids from 50 patients with early stage non-small cell lung cancer before and after surgical resection. The primary Objective is to identify cancer specific metabolome in body fluids - sputum, exhaled breath condensate, blood and urine of the patients with early stage non-small. cell lung cancer (NSCLC) using Magnetic Resonance Spectroscopy (MRS) and Mass Spectroscopy (MS). ConclusionThe trajectory of change in metabolic profile of body fluids before and after surgical resection may have potential clinical applications in lung cancer screening, as biomarkers for disease recurrence and exploration of novel targets for therapeutic intervention.
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