Goulnar Kasymjanova

Prognostic Value of the Six-Minute Walk in Advanced Non-small Cell Lung Cancer

Background: The 6 minute walk (6MW) is usually used to evaluate exercise capacity in a variety of patient populations. We hypothesized that the 6MW would decline after chemotherapy and assessed the prognostic value of this test. Materials and Methods: The 6MW was conducted in newly diagnosed advanced non-small cell lung cancer patients on three different days: twice before (one initial and one prechemotherapy test) and once after two cycles of chemotherapy. Results: Sixty-four patients were enrolled and 45 (70%) completed the study. For patients who dropped out the distance on initial 6MW was 361 m (SD 99) compared with 445 m (SD 85) for completers (p = 0.004). In the 45 completers, the mean 6MW decreased significantly after two cycles. There was a clinically significant (>54 m) decline in 6MW in 13 patients (29%), and an improved/unchanged 6MW in 32 patients (71%). For patients who walked <400 m on initial 6MW, rates of drop out were significantly higher (p = 0.02), progression of disease was statistically more frequent (p = 0.03), and median survival was significantly shorter: 6.7 months (95% confidence interval 2.6–10.8) compared with 13.9 months (95% confidence interval 10.0–17.8) in patients walking ≥400 m (p = 0.01). An initial 6MW of ≥400 m was the only variable with a significant effect on survival in a Cox regression after adjusting for all known covariates of interest. Conclusions: The 6MW declines significantly after two cycles of chemotherapy. This decline may have been even greater as patients with lower 6MW were more likely to drop out of the study. An initial 6MW ≥400 m might be a useful prognostic factor for survival in patients with advanced non-small cell lung cancer.

High risk of deep vein thrombosis in patients with non-small cell lung cancer: a cohort study of 493 patients.

Introduction: The risk of symptomatic deep vein thrombosis (DVT) among patients with non-small cell lung cancer (NSCLC) has not been well studied. We conducted a retrospective cohort study of patients with NSCLC to determine the incidence of DVT and to characterize predictors of DVT in patients with NSCLC. Methods: The pulmonary oncology database of the Sir Mortimer B. Davis–Jewish General Hospital contains prospectively collected clinical data on lung cancer patients since January 1, 1997. We identified all consecutive patients with histologically confirmed new diagnoses of NSCLC between January 1, 1997 and December 31, 2004, and we determined the occurrence of an objectively defined DVT. Data on clinical and tumor characteristics were collected and compared among patients with DVT and patients without DVT. Results: Of the 493 NSCLC patients included in the cohort for a total of 634 person-years, 67 (13.6%) patients developed objectively confirmed DVTs, with an incidence of 110 cases (95% confidence interval [CI] 80, 130) per 1000 person-years. An adjusted multivariable regression analysis showed that advanced stage (rate ratio [RR] 2.63, 95% CI 1.38, 5.00) and male sex (RR 1.75, 95% CI 1.03–2.94) were independent predictors of DVT. Conclusions: Our results show a high incidence of DVT in NSCLC patients. Advanced stage and, to a lesser extent, male sex, are important predictors of DVT. Trials to evaluate the use of prophylactic anticoagulant treatments in patients with NSCLC should be conducted.

Prevalence of emotional distress in newly diagnosed lung cancer patients.

Goals of workDistress is defined by the National Comprehensive Cancer Network as a multifactorial unpleasant emotional experience of a psychological, social, and/or spiritual nature that may interfere with the ability to cope effectively with cancer. We investigated the prevalence and associated symptoms of distress in newly diagnosed lung cancer patients.Patients and methodsBetween November 2005 and July 2007, 98 newly diagnosed lung cancer patients completed an assessment. The Distress Thermometer (DT) and Edmonton Symptom Assessment Scale (ESAS) were used as screening tools.Main resultsFifty (51%) patients reported clinically significant distress (≥4) on the DT. Of those, 26 (52%) patients reported high levels of depression, nervousness, or both on ESAS. The remaining 24 (48%) patients had elevated levels of distress but no significant depression or nervousness. A correlation between the DT and the total ESAS score was observed (Pearson correlation = 0.46). The ten items of the ESAS together explained 46% of the variability in DT scores. The depression and nervousness ESAS items were significant predictors of DT score (p < 0.01 for both items). However, once the two psychosocial items, depression and nervousness, were removed from the total ESAS score, leaving only physical symptoms and the sleeplessness item, the predictive power of the model decreased to R² = 0.12.ConclusionsThe prevalence of distress in lung cancer patients is high. The DT appears to discriminate between physical and emotional distress. This easily measured score may determine which patients require further intervention for emotional distress.

Should Patient-Rated Performance Status Affect Treatment Decisions in Advanced Lung Cancer?

Introduction: The Eastern Cooperative Oncology Group (ECOG) score is a well known prognostic factor and almost always used to determine eligibility for clinical trials. The patient-rated performance status score (Pt-PS), section of the patient generated subjective global assessment scale, has identical criteria to the physician-rated ECOG scale (MD-PS). We compared the Pt-PS with MD-PS in patients with advanced non-small cell lung cancer and compared the effect of each rating on eligibility for a hypothetical clinical trial. Methods: Consecutive patients with newly diagnosed advanced non-small cell lung cancer completed a patient generated subjective global assessment self-rated questionnaire, which was then correlated (kappa statistic) with the ECOG PS recorded at the same time. Patients were treated with standard chemotherapy. Survival was determined using Kaplan-Meier statistics. Results: One hundred nine patients (M:F-54:55) were recruited. Pt-PS differed from MD-PS in 59 (54%) instances (p = 0.0001). When scores were not congruent, 41/59 (69%) patients evaluated themselves as having a worse PS than the physician’s rating. Pt-PS was 0 to 1 in 60 (55%) patients whereas MD-PS was 0 to 1 in 78 (72%) patients. The functional status irrespective of evaluator was predictive of survival (p = 0.001 for MD-PS and p = 0.001 for Pt-PS). However, the median survival in those with MD-PS ≥2 was 3.3 (CI; 1.7-4.9) months whereas individuals with Pt-PS ≥2 had a median survival of 6.2 (CI; 5.4-6.9) months. Conclusions: Pt-PS and MD-PS were not congruent in over half of the cases, with Pt-PS scores usually poorer. Almost half the patients would have excluded themselves from a hypothetical clinical trial (Pt-PS ≥2). This requires prospective evaluation.

Flexible modeling improves assessment of prognostic value of C-reactive protein in advanced non-small cell lung cancer

Background:C-reactive protein (CRP) is gaining credibility as a prognostic factor in different cancers. Coxs proportional hazard (PH) model is usually used to assess prognostic factors. However, this model imposes a priori assumptions, which are rarely tested, that (1) the hazard ratio associated with each prognostic factor remains constant across the follow-up (PH assumption) and (2) the relationship between a continuous predictor and the logarithm of the mortality hazard is linear (linearity assumption).Methods:We tested these two assumptions of the Coxs PH model for CRP, using a flexible statistical model, while adjusting for other known prognostic factors, in a cohort of 269 patients newly diagnosed with non-small cell lung cancer (NSCLC).Results:In the Coxs PH model, high CRP increased the risk of death (HR=1.11 per each doubling of CRP value, 95% CI: 1.03–1.20, P=0.008). However, both the PH assumption (P=0.033) and the linearity assumption (P=0.015) were rejected for CRP, measured at the initiation of chemotherapy, which kept its prognostic value for approximately 18 months.Conclusion:Our analysis shows that flexible modeling provides new insights regarding the value of CRP as a prognostic factor in NSCLC and that Coxs PH model underestimates early risks associated with high CRP.

Characteristics and outcomes of medulloblastoma in adults

Adult medulloblastoma is a rare disease for which there is no internationally accepted standard of care. Treatment regimens have typically been modeled after pediatric protocols. We sought to review the presentation, management, and outcome of patients with adult medulloblastoma treated at the McGill University teaching hospitals over the past 18 years.

The potential role for acupuncture in treating symptoms in patients with lung cancer: an observational longitudinal study

BACKGROUND Most lung cancer patients experience multiple symptoms related either to the disease or its treatment. The commonly reported symptoms are pain, depression, anxiety, nausea, and poor well-being. The aim of the present study was to evaluate the effect of acupuncture as a potential treatment modality in symptomatic lung cancer patients. METHODS This prospective observational study enrolled 33 lung cancer patients from the Peter Brojde Lung Cancer Centre between August 2010 and May 2012. All patients received 45-minute sessions of acupuncture, 1-2 times weekly for a minimum of 4 sessions. Symptom severity was assessed using the Edmonton Symptom Assessment System (esas) before and after completion of acupuncture. RESULTS The study cohort included 30 patients with non-small- cell lung cancer and 3 with small-cell lung cancer. Mean age was 62 years (range: 36-88 years); 17 of the patients were women. Most of the patients had advanced-stage cancer (73%) and good performance status (Eastern Cooperative Oncology Group 0-1: 88%). Of these patients, 67% received anticancer treatment (chemotherapy or radiotherapy, or both) with acupuncture. Of the remaining 10 patients, 8 received acupuncture after a complete surgical resection of their tumour, and because of their advanced age, 2 received acupuncture and best supportive care. The median number of acupuncture sessions was 7 (interquartile range: 4-13 sessions). Statistically significant improvements in pain, appetite, nausea, nervousness, and well-being were observed. A clinically important improvement (2 points on the esas) was reported by 61% of patients for pain and by 33% for well-being. A significant positive correlation between improved well-being and the number of acupuncture sessions was observed. This correlation remained significant even after controlling for treatment and narcotic use. Receiver operating characteristic analysis demonstrated that a minimum of 6 acupuncture sessions are required for a 70% chance of a clinically important improvement in well-being. CONCLUSIONS The present study is the first to demonstrate that acupuncture may be an effective approach for improving symptoms-in particular, pain and well-being-in lung cancer patients. Acupuncture is a safe and minimally invasive procedure, and it is potentially useful even in patients undergoing anticancer treatment.

Montreal prognostic score: estimating survival of patients with non-small cell lung cancer using clinical biomarkers.

Background:For evidence-based medical practice, well-defined risk scoring systems are essential to identify patients with a poor prognosis. The objective of this study was to develop a prognostic score, the Montreal prognostic score (MPS), to improve prognostication of patients with incurable non-small cell lung cancer (NSCLC) in everyday practice.Methods:A training cohort (TC) and a confirmatory cohort (CC) of newly diagnosed patients with NSCLC planning to receive chemotherapy were used to develop the MPS. Stage and clinically available biomarkers were entered into a Cox model and risk weights were estimated. C-statistics were used to test the accuracy.Results:The TC consisted of 258 patients and the CC consisted of 433 patients. Montreal prognostic score classified patients into three distinct groups with median survivals of 2.5 months (95% confidence interval (CI): 1.8, 4.2), 8.2 months (95% CI: 7.0, 9.4) and 18.2 months (95% CI: 14.0, 27.5), respectively (log-rank, P<0.001). Overall, the C-statistics were 0.691 (95% CI: 0.685, 0.697) for the TC and 0.665 (95% CI: 0.661, 0.670) for the CC.Conclusion:The MPS, by classifying patients into three well-defined prognostic groups, provides valuable information, which physicians could use to better inform their patients about treatment options, especially the best timing to involve palliative care teams.

Six Minute Walk Distance Is a Predictor of Survival in Patients with Chronic Obstructive Pulmonary Disease Undergoing Pulmonary Rehabilitation

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a progressive and distressing disease with a trajectory that is often difficult to predict. OBJECTIVE To determine whether initial 6 min walk distance (6MWD) or change in 6MWD following inpatient pulmonary rehabilitation (PR) predicted survival. METHODS Patients referred for PR in 2010 were studied in a retrospective chart review. Measures of 6MWD before and following PR were recorded. Initial 6MWD was categorized as ≥250 m, 150 m to 249 m and ≤149 m. Government databases provided survival status up until December 2013 and survival analyses were performed. Initial 6MWD and a minimally important difference (MID) of ≥30 m were used for survival analysis. RESULTS The cohort consisted of 237 patients (92 men, 145 women) with severe COPD. Mean (± SD) forced expiratory volume in 1 s (FEV1) was 0.75±0.36 L, with a mean FEV1/forced vital capacity (FVC) ratio of 0.57±0.16. Overall three-year survival was 58%. Mean survival for the study period as per predefined categories of 6MWD of ≥250 m, 150 m to 249 m and ≤149 m was 42.2, 37.0 and 27.8 months (P<0.001), respectively, with a three-year survival of 81%, 66% and 34% observed, respectively. Overall mean change in 6MWD was 62±57 m, and a minimal improvement of ≥30 m was observed in 72% of patients. In the lowest walking group, early mortality was significantly higher among those who did not achieve minimal improvement. Older age, male sex and shorter initial 6MWD were negative predictors of survival. CONCLUSION In patients with severe COPD, initial 6MWD was predictive of survival. Overall survival at three years was only 58% and was especially poor (34%) in patients with low (<150 m) initial walk distance.

Quality of life, symptom status and physical performance in patients with advanced non-small cell lung cancer undergoing chemotherapy: an exploratory analysis of secondary data

OBJECTIVES Our objectives were: (a) to identify predictors of change in health-related quality of life (HRQOL) in patients with advanced non-small cell lung cancer (NSCLC) undergoing chemotherapy; and (b) to characterize symptom status, nutritional status, physical performance and HRQOL in this population and to estimate the extent to which these variables change following two cycles of chemotherapy. METHODS A secondary analysis of a longitudinal observational study of 47 patients (24 men and 23 women) with newly diagnosed advanced NSCLC receiving two cycles of first-line chemotherapy was performed. Primary outcomes were changes in HRQOL (physical and mental component summaries (PCS and MCS) of the 36-item Short-Form Health Survey (SF-36)). Predictors in the models included pre-chemotherapy patient-reported symptoms (Schwartz Cancer Fatigue Scale (SCFS) and Lung Cancer Subscale), nutritional screening (Patient-Generated Subjective Global Assessment) and physical performance measures (6-min Walk Test (6MWT), one-minute chair rise test and grip strength). RESULTS Mean SF-36 PCS score, 6MWT distance and grip strength declined following two cycles of chemotherapy (p<0.05). Multiple linear regression modelling revealed pre-chemotherapy SCFS score and 6MWT distance as the strongest predictors of change in the mental component of HRQOL accounting for 13% and 9% of the variance, respectively. No significant predictors were found for change in the physical component of HRQOL. CONCLUSIONS Pre-chemotherapy 6MWT distance and fatigue severity predicted change in the mental component of HRQOL in patients with advanced NSCLC undergoing chemotherapy, while physical performance declined during treatment. Clinical management of these factors may be useful for HRQOL optimization in this population.