V. Cohen

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.

Systemic cancer therapy: achievements and challenges that lie ahead

In the last half of the century, advances in the systemic therapy of cancer, including chemotherapy, hormonal therapy, targeted therapy, and immunotherapy have been responsible for improvements in cancer related mortality in developed countries even as the population continues to age. Although such advancements have yet to benefit all cancer types, systemic therapies have led to an improvement in overall survival in both the adjuvant and metastatic setting for many cancers. With the pressure to make therapies available as soon as possible, the side-effects of systemic therapies, in particular long-term side-effects are not very well characterized and understood. Increasingly, a number of cancer types are requiring long-term and even lifelong systemic therapy. This is true for both younger and older patients with cancer and has important implications for each subset. Younger patients have an overall greater expected life-span, and as a result may suffer a greater variety of treatment related complications in the long-term, whereas older patients may develop earlier side-effects as a result of their frailty. Because the incidence of cancer in the world will increase over the next several decades and there will be more people living with cancer, it is important to have an understanding of the potential side-effects of new systemic therapies. As an introductory article, in this review series, we begin by describing some of the major advances made in systemic cancer therapy along with some of their known side-effects and we also make an attempt to describe the future of systemic cancer therapy.

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.

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.

Life-threatening tinnitus

A 68-year-old woman presented in October, 1998, with an 8-week history of tinnitus and dizziness. She had no history of cardiovascular, or neurological disease. Computed tomography (CT) scan of the head was not diagnostic. She returned 3 weeks later with new symptoms of altered taste sensation, dysphagia, left-sided numbness, unsteady gait, and diplopia. She had no vertigo, nausea, vomiting, fevers, headaches, or anorexia. There was no history of changes in personality, mood, or cognitive decline, or of seizures. She had lost 7 kg in weight over the past 6 months. Heart rate, blood pressure, temperature, mental state examination and speech were normal. The pupils were reactive and symmetrical. Fundoscopic examination was normal. She had a slow gaze to the left with a 1 syndrome (one eye was fixed in the midline, the other eye could only make abducting movements with horizontal nystagmus in the direction of the abduction). She had decreased left facial sensation and a diminished left corneal reflex. The cranial nerves were otherwise normal. Muscle tone and power were normal. Heel to skin testing was adequate but finger to nose was dysmetric on the left side. She had decreased light touch sensation on the left side of the body. Deep tendon reflexes were normal and symmetrical and the plantar response was flexor bilaterally. The patient’s gait was wide based with severe truncal ataxia. Full blood count, peripheral blood smear, coagulation tests, a biochemistry profile, serum vitamin B12 and folate, thyroid function tests, erythrocyte sedimentation rate, Creactive protein, antinuclear antibodies, antineutrophil cytoplasmic antibody, rheumatoid factor, complement levels for C3 and C4, serum protein electrophoresis, cryoglobulins, and quantitative serum immunoglobulins were normal. Cerebrospinal fluid (CSF) analysis showed protein 0·65 g/L and glucose 4·2 mmol/L, 139 red cells and nine white cells per L (mostly lymphocytes with a few atypical cells). There was no immunological evidence of syphilis (VDRL). CSF cultures and polymerase chain reactions for herpes and cytomegalovirus were negative. Oligoclonal bands were absent. Doppler study of carotid and vertebro-basilar arteries was normal. Gadoliniumenhanced magnetic resonance imaging (MRI) of the head showed bilateral contrast enhancement in the medial aspects of the temporal lobes in the amygdala and hippocampi, as well as in the posterior aspect of the medulla, pons, and midbrain (figure). The imaging was diagnostic for limbic and bulbar encephalitis. CASE REPORT

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.

HSP90 as a novel molecular target in non-small-cell lung cancer.

Lung cancer remains the most lethal cancer, with over 160,000 annual deaths in the USA alone. Over the past decade, the discovery of driver mutations has changed the landscape for the treatment of non-small-cell lung cancer (NSCLC). Targeted therapies against epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) have now been approved by the Food and Drug Administration as part of the standard first-line treatment of NSCLC. Despite good initial responses, most patients develop resistance within 8–12 months and have disease progression.