David Small

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 correlationu2009=u20090.46). 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 (pu2009<u20090.01 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 R²u2009=u20090.12.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.

International differences in epidemiology of lung adenocarcinoma

In Europe, the squamous cell carcinoma is the most frequent non-small cell lung cancer (NSCLC) subtype and until now, no increase in incidence of lung adenocarcinoma (ADC) has been described (except in the Netherlands), in contrast to North America where ADC predominates. Our aim was to compare the percentage of ADC in Montreal (MTL), Canada, with that in Strasbourg (STBG), France. We prospectively identified patients with NSCLC in MTL and in STBG over an 8-month period and described the distribution of NSCLC by sex, age, subtype and smoking history. A total of 172 patients in MTL and 166 in STBG were identified. The male/female ratio was significantly different in STBG (12:1) and in MTL (2:1). The percentage of ADC was significantly higher in MTL (40%) than in STBG (30%). This difference is partly due to the higher number of women with NSCLC in Montreal combined with the predominance of ADC in women. The proportion of ADC decreased with age in STBG, but was similar in each age category in MTL. In STBG, most women with NSCLC had never smoked (69%), in contrast to MTL where only 16% of women had never smoked. In conclusion, ADC is more frequent in MTL than in STBG. This is partly due to the higher number of women with NSCLC in MTL combined with the predominance of ADC in women. The greatest proportion of ADC subtype in the youngest cohorts of men in STBG suggests that ADC may be on the rise in this city.

Screening for depressive symptoms in patients with unresectable lung cancer

IntroductionEarly identification of psychological distress and depression is important to optimise the quality of life in patients with advanced non-small cell lung cancer (NSCLC). The prevalence of depression may vary, depending on the time since diagnosis of cancer, results of the treatment and the prognosis. The purpose of this study was to compare the efficacy of a self-administered screening tool (Hospital Anxiety and Depression Scale (HADS)) with a health professional administered tool (Montgomery–Asberg Depression Rating Scale (MADRS)) and to explore the variability of major affective symptoms in patients with unresectable lung cancer during the initial 7–8xa0weeks of chemotherapy treatment for their illness.Material and methodsPatients with newly diagnosed unresectable lung cancer were screened on four occasions for anxiety and depressive symptoms simultaneously using the self-rated HADS and the MADRS administered by a psycho-oncologist or a trained research associate. The first assessment was done within 1xa0week of diagnosis and was repeated on 3 occasions during the initial 2xa0cycles of chemotherapy.ResultsForty-nine patients, aged 38–82xa0years (median age 63xa0years) were enrolled. All patients had advanced NSCLC (stages 3A, 3B and 4) and 61% (30 patients) had an ECOG performance status (PS) of 1 or greater. The point prevalence of depression measured by an interviewer using the MADRS at visits 1–4 was 49%, 51%, 47%, and 41%, respectively. The point prevalence of self-reported depression (HADS) was significantly (pu2009<u20090.001) lower at each assessment point (18%, 20%, 6%, 12%) compared to health professional detected depression (MADRS). Although MADRS and HADS showed very strong (Pearson’s correlationu2009=u20090.8) and significant (pu2009<u20090.001) correlation, the concordance rate in identifying the same cases of depression was only 54%.Clinical implication and conclusionThe prevalence of depression among advanced lung cancer patients is high and varies very little during the first 2xa0cycles of chemotherapy. Among a variety of tools available for the screening of depression, a semi-structured interview is more effective at identifying clinically significant depression than a self-administered questionnaire.

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

Absence of toxicity with hypofractionated 3-dimensional radiation therapy for inoperable, early stage non-small cell lung cancer.

PurposeHypofractionated radiotherapy may overcome repopulation in rapidly proliferating tumors such as lung cancer. It is more convenient for the patients and reduces health care costs. This study reports our results on patients with medically inoperable, early stage, non-small cell lung cancer (NSCLC) treated with hypofractionation.Materials and methodsStage T1-2N0 NSCLC patients were treated with hypofractionation alone, 52.5 Gy/15 fractions, in 3 weeks, with 3-dimensional conformal planning. T1-2N1 patients with the hilar lymphnode close to the primary tumor were also eligible for this treatment. We did not use any approach to reduce respiratory motion, but it was monitored in all patients. Elective nodal radiotherapy was not performed. Routine follow up included assessment for acute and late toxicity and radiological tumor response. Median follow up time was 29 months for the surviving patients.ResultsThirty-two patients with a median age of 76 years, T1 = 15 and T2 = 17, were treated. Median planning target volume (PTV) volume was 150cc and median V16 of both lungs was 13%. The most important finding of this study is that toxicity was minimal. Two patients had grade ≤ 2 acute pneumonitis and 3 had mild (grade 1) acute esophagitis. There was no late toxicity. Actuarial 1 and 2-year overall survival rates are 78% and 56%, cancer specific survival rates (CSS) are 90% and 74%, and local relapse free survival rates are 93% and 76% respectively.Conclusion3-D planning, involved field hypofractionation at a dose of 52.5 Gy in 15 daily fractions is safe, well tolerated and easy radiation treatment for medically inoperable lung cancer patients. It shortens by half the traditional treatment. Results compare favorably with previously published studies. Further studies are needed to compare similar technique with other treatments such as surgery and stereotactic radiotherapy.

Phase II study of weekly plitidepsin as second-line therapy for small cell lung cancer

OBJECTIVEnTo evaluate the antitumor activity and safety profile of plitidepsin administered as a 1h weekly intravenous (i.v.) infusion of 3.2mg/m(2) to patients with small cell lung cancer (SCLC) who relapsed or progressed after one line of chemotherapy.nnnPATIENTS AND METHODSnThis was a multicenter, open-label, single-arm, exploratory, phase II clinical trial. Treatment lasted until disease progression, unacceptable toxicity, patient refusal or treatment delay for >2 weeks. Objective response rate (primary efficacy endpoint) was evaluated according to response evaluation criteria in solid tumors (RECIST). The rate of stable disease (SD) lasting for at least 6 months and time-to-event variables were secondary endpoints of efficacy. Toxicity was assessed using National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 2.0.nnnRESULTSnTwenty pretreated SCLC patients (median age, 60 years) with extensive (n = 13) or limited-stage disease (n = 7) received a total of 24 treatment cycles (median, one cycle per patient; range, 1-2). Objective tumor responses were not observed and only one of the 17 evaluable patients had SD. With a median follow-up of 11.8 months, the progression-free survival and the median overall survival were 1.3 months and 4.8 months, respectively. The most troubling or common toxicities were fatigue, muscle weakness, lymphopenia, anemia (no patients showed neutropenia), and asymptomatic, non-cumulative increase of transaminases levels and alkaline phosphatase.nnnCONCLUSIONnThis clinical trial shows that a cycle of 1h weekly i.v. infusion of plitidepsin (3.2mg/m(2)) was generally well tolerated other than fatigue and muscle weakness in patients with pretreated SCLC. One patient died due to multi-organ failure. The absence of antitumor activity found here precludes further studies of this plitidepsin schedule as second-line single-agent treatment of SCLC.

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

BACKGROUNDnMost 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.nnnMETHODSnThis 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnThe 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.