Harvey Kreisman

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.

Small cell lung cancer presenting as a solitary pulmonary nodule

Small cell lung cancer (SCLC) rarely presents radiographically as a solitary pulmonary nodule (SPN). Twenty‐five patients with this feature were identified among 408 individuals with SCLC at McGill University (Montreal, Quebec) from 1979 through 1984. Of these, 15 (60%) were confirmed on pathologic review as SCLC (ten intermediate cell, four oat cell, one indeterminate). Pathologic review of a control group comprising 24 other limited‐disease patients who were long‐term survivors (> 20 months) confirmed 20 (84%) as SCLC (eight intermediate cell, 12 oat cell). Ten of the 15 patients with SPN were resected whereas five had chemotherapy and/or radiotherapy as primary treatment. Postoperative chemotherapy was administered to most of the resected patients. The median survival of the 15 patients with SPN was 24 months, a significantly longer survival than the other patients with SCLC. This improved prognosis in patients with SPN may be due to smaller initial tumor burden or to a fundamental biologic difference between SPN and other forms of SCLC.

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.

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.

The Solitary Pulmonary Nodule — Decision Analysis

A solitary pulmonary nodule is a finding on chest X-ray showing a single circumscribed mass in the lung. This finding is usually not associated with any other abnormality or any Symptoms and is often first noticed on routine examination. Many disease processes, particularly lung cancer, tuberculosis, and fungal infections of the lung may cause such a nodule. Though biopsy with a fine needle may be used to establish the nature of the nodule, often this technique is unavailable, or yields no definite result. In this case thoracotomy is needed to obtain a diagnosis. The advantages of surgery are that it assures a definite diagnosis and is also the best treatment for lung cancer which presents as a solitary nodule. However, the potential long-term benefit of surgery must be balanced against both the immediate risk of the operation and the advantage of not operating on those patients who have a benign nodule. At present the physician must decide the case before surgery. Without the benefit of precise quantitative data or the formal techniques to apply such data to an individual patient.

Analysis of neuroendocrine markers, HER2 and CEA before and after chemotherapy in patients with stage IIIA non-small cell lung cancer: a Cancer and Leukemia Group B study.

Several studies have suggested that biochemical or molecular markers examined in non-small cell lung cancer carry prognostic or treatment response information. Non-small cell lung cancer patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of HER2 (c-erbB-2), a membrane-bound receptor with tyrosine kinase activity, has been associated with shortened survival. The Cancer and Leukemia Group B (CALGB) performed a study of patients with stage IIIA (N2 nodes positive) non-small cell lung cancer in which patients received initial chemotherapy followed by surgery, then post-operative therapy consisting of sequential chemotherapy and radiation therapy. Since all patients underwent mediastinoscopy, this provided an opportunity to compare pre- and post-chemotherapy tumor specimens to test the hypothesis that these proteins would predict treatment response. In particular, we hypothesized that the post-chemotherapy specimens would be enriched for NE marker negative cells because of the increased sensitivity of NE positive cells to chemotherapy. We performed immunohistochemical analysis for a panel of NE markers [neuron-specific enolase (NSE), Leu-7, chromogranin A (ChrA), synaptophysin (Syn)], HER2 and CEA to determine if there was an effect of therapy on the percentage of cells expressing these markers. Secondary endpoints were a correlation with chemotherapy response and survival. Slides were scored for intensity (0-4) and percentage of cells positive (0-4). Of 61 eligible patients, there were 38 with both pre- and post-chemotherapy specimens. When both intensity of staining and percentage of positive cells were considered, post-chemotherapy specimens had a higher percentage of positive NE markers compared with pre-chemotherapy. In addition, there was no correlation between NE marker, HER2 or CEA expression (prior to or post treatment) and response to chemotherapy or survival. These data do not support the hypothesis that NE positive tumor cells are preferentially killed by chemotherapy in patients with stage IIIA non-small cell lung cancer.

Fatal pulmonary toxicity following oral etoposide therapy

Oral etoposide has considerable activity in small cell lung cancer and the low risk of toxicity has resulted in the frequent prescription of this agent in elderly or infirmed patients. We describe a case of fatal pulmonary toxicity following the administration of oral etoposide. This is the first report of biopsy-proven pulmonary toxicity associated with this agent.

Cisplatin-carboplatin therapy in extensive non-small cell lung cancer: a Cancer and Leukemia Group B study

The response to cisplatin in non-small cell lung cancer (NSCLC) is limited by the renal and neurological toxicities of this agent. Carboplatin has modest activity in NSCLC and when given in conventional doses has a different spectrum of toxicity. Both drugs were administered to 76 eligible patients with advanced NSCLC. No patient had been previously treated with chemotherapy. Cisplatin 50 mg/m2 and carboplatin 350 mg/m2 were administered every 28 days until disease progression occurred. There was 1 complete response and the overall response rate among the 68 evaluable for response patients was 13%. Neither histological subtype nor initial performance status was a significant factor influencing response. Median survival was 5.1 months with significant differences based on initial performance status but not on histological subtype. Severe or life-threatening leukopenia and thrombocytopenia occurred in 23% and 36% of the 76 patients, respectively. There were 2 toxic deaths, 1 each due to infection and haemorrhage. The efficacy of this combination is not different from that of carboplatin alone, and the combination may be of greater benefit in patients with more responsive tumours than NSCLC.

Multifocal relapse after concurrent chemotherapy and radiotherapy of small cell lung cancer

Twenty‐one patients with small cell lung cancer (SCLC) were treated with cyclophosphamide (1250 mg/m2), Adriamycin (40 mg/m2), vincristine (2 mg) every three weeks. Thoracic radiotherapy (3000 rad: 10 or 15 fractions) began four weeks after starting chemotherapy. Patients with brain metastases received cranial irradiation. Thirteen of 19 evaluable patients responded to therapy (four complete responses). Sixteen of 19 had significant intrathoracic response (eight complete). Of the three patients without an intrathoracic tumor response, two had simultaneous progression in systemic locations and only one had intrathoracic progression preceding systemic progression. Intrathoracic relapse preceded systemic relapse in two patients, was simultaneous with it in six and followed systemic relapse in four others. Therefore only three patients had intrathoracic tumor progression or relapse preceding systemic progression or recurrence. The more intensive course of radiotherapy was significantly better in preventing intrathoracic tumor progression. Although intrathoracic tumor control is important, primary failure of therapy or relapse appears to be multifocal. Future attention must be directed toward control of mutiple potential sites of relapse.

P-660 Screening for depressive symptoms in patients with unresectable lung cancer

Introduction Early 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 7–8 weeks of chemotherapy treatment for their illness.