Prognostic factors in elderly patients with non-small cell lung cancer: a two-center experience

Non-small cell lung cancer (NSCLC) is usually at advanced stage when it is diagnosed. There is no consensus about the standard treatment in elderly patients with advanced NSCLC. Generally, data regarding elderly patients with NSCLC are withdrawn from general NSCLC studies based on subgroup analyses and suggestions. We evaluated prognostic factors in elderly patients with advanced NSCLC. We reviewed retrospectively 338 patients from August 2005 to July 2009 in two centers in Turkey. Medical records of the patients ≥65 years with advanced NSCLC were collected. Collected data included demographic informations, clinical assessments and information on treatment, toxicities and outcomes. Survival was estimated by using Kaplan–Meier method and prognostic factors were evaluated with log-rank and Cox regression tests. The median overall survival (OS) for the entire group was 15.4 months (95% CI: 12.7–18.0). In univariate analysis, weight loss, stage, combination therapy, second-line chemotherapy and tumor response (P < 0.01) and performance status significantly affected OS (P < 0.05). The median progression-free survival (PFS) was 10 months (95% CI: 8.4–11.6). In univariate analysis, there was only a significant association between tumor response and PFS (14.6 vs. 8.5 months; P < 0.001). Multivariate analysis showed that only response to therapy was an important prognostic factor for OS (P < 0.001). Survival of elderly patients with advanced NSCLC is significantly influenced by performance status, weight loss, stage, combination therapy, second-line chemotherapy and response to therapy. Not only age but also these factors may be kept in mind in the treatment planning of the elderly patients with NSCLC. These results may be of benefit in changing clinical practice in elderly patients with NSCLC who are often undertreated.     

The role of PET-CT in the differential diagnosis of thymic mass after treatment of patients with lymphoma

Thymic hyperplasia is a common phenomenon in both children and young adults after chemotherapy and may explain the finding of a mediastinal mass in patients with malignant lymphoma after complete remission. In the present study, we report 5 cases with malignant lymphoma presenting with a mediastinal mass on CT scan after completion of chemotherapy diagnosed as thymic hyperplasia by PET-CT imaging. We retrospectively analyzed 5 patients who presented with anterior mediastinal masses a median of 4 months (range 3–6) after achieving complete remission following successful treatment for malignant lymphoma. Three patients were diagnosed with Hodgkin’s lymphoma (HL) and the others with non-Hodgkin’s lymphoma (NHL). The median age of the patients was 23 (range of 18–47). PET-CT was performed on these patients to determine the characteristics of a mass which had been detected on CT. PET-CT was performed for all patients, and the thymic masses demonstrated only mild FDG uptake considered to be consistent with thymic hyperplasia. During a median of 24 months of follow-up, all patients were recurrence-free with a median survival of 15 months (range 10–26 months). It is important to be aware of the possibility of thymic hyperplasia after chemotherapy to avoid misdiagnosis or over-staging of disease, as well as unnecessary biopsies, especially when the presenting anterior mediastinal mass was originally located near the thymus on CT scan. Mild FDG PET uptake was sufficient for the diagnosis of benign disease in the cases in this study.     

Prognostic factors in small cell lung cancer

In order to find out prognostic factors and treatment results in small cell lung cancer (SCLC), 40 patients diagnosed in one year period were prospectively analysed. Following history and physical examination, patients were grouped according to ECOG performance scale and underwent Chest X-ray and thoracic computerized tomography (CT). Complete blood count, biochemical analyses, tumor markers were taken. Abdominal USG or CT, bone scintigraphy, cranial CT or MRI and bone marrow biopsy were made for detection of metastases. Limited stage patients received chemotherapy and thoracic RT, whereas cases with extensive disease received chemotherapy. Nineteen cases had limited and 21 had extensive disease. When laboratory findings between 2 stages were compared, LDH, SGOT and GGT were significantly higher in extensive stage (p= 0.005, 0.015, 0.001, respectively). Overall median survival was 6 +/- 1 months, cumulative survival in 6 and 12 months were 39% and 20.72%, respectively. Median survival was 10 +/- 2 months in limited stage and 3 +/- 1 months in extensive stage, with a statististically significant difference. Univariate analyses showed that incresed LDH, CA15-3, GGT and SGOT levels, hipoproteinemia and poor performance scale were poor prognostic signs (p= 0.024, 0.032, 0.047, 0.013, 0.021 ve 0.013, respectively), however multivariate analyses revealed no significant difference. Other blood tests, pleural effusion, age, mediastinal lymph node metastases and weight loss had no prognostic effect. Stage was found to be progniostic factor with both univariate and multivariate analyses (p= 0.045).     

5-Fluorouracil induces arterial vasoconstrictions but does not increase angiotensin II levels

Because the mechanisms of 5-Fluorouracil (5-FU) cardiotoxicity have not yet been completely identified, prophylactic options are not available. To our knowledge, there are no published data investigating the use of angiotensin converting enzyme (ACE) inhibitors for 5-Fluorouracil-associated cardiotoxicity. In this study, we aimed to evaluate the influence of 5-FU administration on the diameter of the brachial artery and the levels of angiotensin II. The patients were administered bolus 5-FU/leucovorin in the study group. Angiotensin II and troponin T assays, complete blood cell counts, hepatic and renal function tests were analyzed in five consecutive blood samples in the initiation, just after termination, and on 24, 48, and 72 h after termination of the regimen. Pre- and post-treatment angiotensin II and troponin T assays, complete blood cell counts, hepatic and renal function tests were also analyzed in the control group. Brachial arterial diameters were measured and recorded in all patients before and after the treatment. A total of 59 patients were included in this study. Thirty one out of 59 patients (52.5%) were in the 5-FU study group and the remaining 28 patients (47.5%) were in the control group. Basal and post-treatment brachial artery diameters in the 5-FU study group were 0.436 ± 0.51 and 0.423 ± 0.50 cm, respectively (P = 0.001). The corresponding values in the controls were 0.3954 ± 0.50 and 0.3957 ± 0.49 cm, basal and post-treatment, respectively (P = 0.979). Angiotensin II levels were not changed significantly at serial measurements (P = 0.496). Moreover, the corresponding measurements were not statistically different in both two groups treated with and without 5-FU (P = 0.372). The pathophysiology of 5-FU-induced cardiac toxicity has not yet been elucidated. In the present study, 5-FU-associated vasoconstriction was not dependent on angiotensin II levels, thus we suggest that the prophylactic administration of ACE inhibitors cannot prevent cardiotoxicity in these patients. The underlying mechanisms of cardiotoxicity related to 5-FU might be multifactorial; nevertheless, further prospective investigation for the toxic effects of fluoropyrimidines on the coronary endothelium and myocardium are needed.     

Thrombin-activatable fibrinolysis inhibitor levels in patients with non-small-cell lung cancer

BACKGROUND: An increased incidence of thromboembolic events has been described in patients with cancer. Cancer cells are attributed with producing procoagulant substances such as cysteine protease and tissue factor to activate factor X and factor VII, respectively. However, there are limited data on the pathogenesis behind this hypercoagulability state, and the thrombin generation, fibrinolytic system, and coagulation inhibition system during cancer are largely obscure. In this study, we investigated the changes of different steps of coagulation pathway in patients with non-small-cell lung cancer (NSCLC) and compared the data with those of healthy controls. PATIENTS AND METHODS: Forty-four patients with NSCLC and 36 age-matched controls were recruited for this study. Prothrombin fragment 1 + 2 (F 1 + 2) were used as a marker of thrombin generation; thrombin-activatable fibrinolysis inhibitor (TAFI) immunologic activity level was measured for inhibition of the fibrinolytic system, and tissue factor pathway inhibitor (TFPI) activity was assessed for the coagulation inhibition system. In the patient group, the relationships between TAFI activity levels and patient parameters (age, sex, body mass index [BMI], histopathology, and stage) were evaluated. RESULTS: The TAFI activity, F 1 + 2 levels, and TFPI activity were significantly higher in patients with lung cancer than in subjects in the control group (P < .05; P < .0001; and P < .0001; respectively). However, there were no statistically significant associations between TAFI activity levels and patient age, sex, BMI, histopathology, or stage of disease (P > .05). CONCLUSION: In this study, it was clearly shown that patients with lung cancer have hypercoagulable states and that the pathogenesis of thrombotic events in these patients is multifactorial. Increased TFPI is a reflection of thrombin activity in this patient group. Confirmatory studies with larger patient groups should be performed in this population.     

Efficacy of Iodopovidone Pleurodesis and Comparison of Small-Bore Catheter Versus Large-Bore Chest Tube

Background  To evaluate the efficacy of iodopovidone as an agent for pleurodesis in malignant pleural effusion (MPE) and to compare the efficacy of small-bore catheter (Pleuracan, Braun, Melsungen, Germany) and conventional large-bore chest tube in pleural fluid drainage and sclerotherapy. Methods  Patients with MPE were prospectively consecutively randomized into two groups between August 2004 and February 2007: pleurodesis via conventional (32F) chest tube (group 1) and small-bore catheter (group 2), both using iodopovidone. After 3 months’ follow-up, response rates (complete or partial), complication rates, and duration of procedures within whole group, group 1, and group 2 were compared. Statistical analyses were performed by Mann-Whitney U, χ², and Fisher’s exact test. Results  Forty-three pleurodeses were performed in 41 patients. The response was complete in 26 (60.5%) and partial in 12 (27.9%), and the overall success rate was 88.4%. The response rate was not associated with the type of inserted tube (P = .750), pleural fluid pH (P = .290), or pleural fluid lactate dehydrogenase (P = .727). In group 1 (n = 20), 12 demonstrated complete and 6 demonstrated partial response, with a 90% success rate; success was 86.9% in group 2, with complete response in 14 and partial response in 6 patients. Success rates were similar in the two groups (P = 1.000). Of 43 procedures, complications were observed in 14 (32.5%), and complication rates were 35% and 30.4% in groups 1 and 2, respectively (P = .750). The most frequent complication was pain (16.2%), followed by fever, subcutaneous emphysema, dyspnea, and hypotension. Conclusion  Iodopovidone is an effective, inexpensive, safe, and easily available alternative in chemical pleurodesis in MPE. The success rates of pleurodesis were found to be similar regardless of the type of the tube inserted.     

HPV DNA frequency and subset analysis in human breast cancer patients' normal and tumoral tissue samples

Viruses are known to be associated with human malignancies, e.g., Epstein-Barr virus, human papillomavirus (HPV) and human T-cell leukemia virus type I. We conducted a prospective study to define the role of HPV in breast cancer. The malignant and normal breast tissue samples of 50 consecutive breast cancer patients were obtained postoperatively. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Thirty-seven samples (74%) of tumoral breast tissue expressed HPV-DNA, 16 normal breast tissue samples (32%) were positive as well. There was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples. HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (54.4%) and in 9 of the HPV-DNA positive normal tissue (56.3%). HPV-33 also was detected in 35 (94.6 %) of the HPV-DNA positive tumoral tissue and in 14 (87.5 %) of the HPV-DNA positive normal tissue samples. HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Additional studies looking at HPV and HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer.     

Extrapulmonary small cell carcinoma: multimodality treatment results

AIMS AND BACKGROUND: Extrapulmonary small cell carcinoma is a distinct entity that can occur in many sites, and it is pathologically similar to small-cell lung cancer. We report the results of a retrospective study of a multimodality treatment of 16 consecutive patients with a diagnosis of extrapulmonary small-cell carcinoma. METHODS: Primary tumor site was prostate in 2, gallbladder in 2, uterine cervix in 2, liver in 2, endometrium in 1, epididymis in 1, colon in 1, larynx in 1, breast in 1, and unknown primary tumor in 3 patients. Patients' ages ranged from 19 to 79 years (median, 62). Nine patients had limited and 7 had extensive disease. Histologically, 14 were pure extrapulmonary small-cell carcinoma and 2 were mixed with squamous-cell carcinoma. RESULTS: Curative surgery was attempted in 8 patients. Seven patients received local-regional adjuvant radiotherapy. All patients, except the one with a breast primary, were treated with chemotherapy (mostly platinum-based regimens). Overall survival for all patients was 41% and 11% at 2 and 5 years, respectively (median survival, 14 months). Median survival for patients with limited disease was 25 months compared to 12 months for patients with extensive disease (P = 0.05). CONCLUSIONS: Treatment results for extrapulmonary small-cell carcinoma are comparable to those of small-cell carcinomas of the lung. Extent of disease is a significant prognostic factor for survival.