Jason Scott Agulnik

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.

Health-related quality of life and utility in patients with advanced non-small-cell lung cancer: a prospective cross-sectional patient survey in a real-world setting.

Background: Non–small-cell lung cancer (NSCLC) has a significant impact on patients’ health-related quality of life (HRQOL). This study aimed to measure health state utility values representing the individual’s preferences for specific health-related outcomes in advanced NSCLC patients and to assess predictive parameters. Methods: We conducted a prospective quality-of-life survey on advanced NSCLC patients in 25 hospitals in Europe, Canada, Australia, and Turkey. HRQOL was assessed using the EuroQol (EQ-5D) questionnaire and EQ-5D utility and EQ-visual analog (EQ-VAS) scores were estimated. Results: Three hundred nineteen patients were recruited of which 263 had evaluable data. Mean utility for progression-free (PF) patients on first-, second-, and third-/fourth-line treatment was 0.71 (SD = 0.24), 0.74 (SD = 0.18), and 0.62 (SD = 0.29), respectively. Mean utility for patients with progressive disease (PD) while on first-, second- and third-/fourth-line treatment was 0.67 (SD = 0.2), 0.59 (SD = 0.34), and 0.46 (SD = 0.38), respectively. Overall, patients with PD had lower mean utility scores than PF patients (0.58 versus 0.70). The results of the EQ-VAS showed that the score decreased with later treatment lines. Patients with PD had a 10-point decrease in VAS scores compared with PF patients (53.7 versus 66.6). The regression analysis revealed that stage IV disease, higher lines of treatment, and health state were significant predictors of utility at the 10% level. Conclusion: 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.

High-Dose Intravenous Vitamin C Combined with Cytotoxic Chemotherapy in Patients with Advanced Cancer: A Phase I-II Clinical Trial

Background Biological 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 Findings We 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. Conclusions Despite 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 Registration ClinicalTrials.gov NCT01050621

A Systemic Review of Resistance Mechanisms and Ongoing Clinical Trials in ALK-Rearranged Non-Small Cell Lung Cancer.

The identification of oncogenic driver mutations in non-small cell lung cancer (NSCLC) has led to a paradigm shift and the development of specific molecular treatments. Tumors harboring a rearranged EML4–ALK fusion oncogene are highly sensitive to therapy with ALK-targeted inhibitors. Crizotinib is the first approved treatment for advanced lung tumors containing this genetic abnormality. In this mini review, we discuss the existing data on crizotinib as well as ongoing trials involving this medication. A brief overview of the known resistance mechanisms to crizotinib will also be presented followed by a summary of the ongoing trials involving next-generation ALK-inhibitors or other targeted therapies in patients with ALK+ NSCLC.

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.

Canadian consensus: inhibition of ALK-positive tumours in advanced non-small-cell lung cancer.

Anaplastic lymphoma kinase (alk) is an oncogenic driver in non-small-cell lung cancer (nsclc). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous nsclc patients and lead to constitutive activation of the alk signalling pathway. ALK-positive nsclc is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the alk pathway prolongs progression-free survival in patients with ALK-positive advanced nsclc. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous nsclc (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted alk inhibitor in the first-line setting is recommended. As patients become resistant to first-generation alk inhibitors, other treatments, including second-generation alk inhibitors can be considered.

Lung cancer care trajectory at a Canadian centre: an evaluation of how wait times affect clinical outcomes

BACKGROUND Lung cancer continues to be one of the most common cancers in Canada, with approximately 28,400 new cases diagnosed each year. Although timely care can contribute substantially to quality of life for patients, it remains unclear whether it also improves patient outcomes. In this work, we used a set of quality indicators that aim to describe the quality of care in lung cancer patients. We assessed adherence with existing guidelines for timeliness of lung cancer care and concordance with existing standards of treatment, and we examined the association between timeliness of care and lung cancer survival. METHODS Patients with lung cancer diagnosed between 2010 and 2015 were identified from the Pulmonary Division Lung Cancer Registry at our centre. RESULTS We demonstrated that the interdisciplinary pulmonary oncology service successfully treated most of its patients within the recommended wait times. However, there is still work to be done to decrease variation in wait time. Our results demonstrate a significant association between wait time and survival, supporting the need for clinicians to optimize the patient care trajectory. INTERPRETATION It would be helpful for Canadian clinicians treating patients with lung cancer to have wait time guidelines for all treatment modalities, together with standard definitions for all time intervals. Any reductions in wait times should be balanced against the need for thorough investigation before initiating treatment. We believe that our unique model of care leads to an acceleration of diagnostic steps. Avoiding any delay associated with referral to a medical oncologist for treatment could be an acceptable strategy with respect to reducing wait time.

The Peter Brojde lung cancer centre: a model of integrative practice.

BACKGROUND The generally poor prognosis and poor quality of life for lung cancer patients have highlighted the need for a conceptual model of integrative practice. Although the philosophy of integrative oncology is well described, conceptual models that could guide the implementation and scientific evaluation of integrative practice are lacking. PURPOSE The present paper describes a conceptual model of integrative practice in which the philosophical underpinnings derive mainly from integrative oncology, with important contributions from Traditional Chinese Medicine (TCM) and the discipline of nursing. The conceptual model is described in terms of its purpose, values, concepts, dynamic components, scientific evidence, clinical approach, and theoretical underpinnings. The model argues that these components delineate the initial scope and orientation of integrative practice. They serve as the needed context for evaluating and interpreting the effectiveness of clinical interventions in enhancing patient outcomes in lung cancer at various phases of the illness. Furthermore, the development of relevant and effective integrative clinical interventions requires new research methods based on whole-systems research. An initial focus would be the identification of interrelationship patterns among variables that influence clinical interventions and their targeted patient outcomes.