Ornella Belvedere

Fatigue: A main component of anemia symptomatology

Fatigue is a common complaint of patients with cancer or other physical or mental disorders. In cancer patients, the estimated prevalence of fatigue is high (about 70% to 90% in different surveys). However, despite the high prevalence and widely recognized clinical relevance of fatigue, few studies have been performed to evaluate the putative causal factors and therapeutic approaches for this condition. The paucity of studies has been mainly because of the lack of proper instruments to quantify this clinical problem. Moreover, fatigue is multifactorial, which makes evaluation of precise relationships with other medical conditions difficult. In particular, fatigue is considered the cardinal symptom of anemia. The pathogenesis of anemia-related fatigue remains unclear, but some suggest that abnormalities in energy metabolism play a role in inducing fatigue. In cancer patients, this effect may be exacerbated by the increased metabolic needs associated with tumor growth. At the clinical level, the relationship between anemia and fatigue is universally accepted. However, early studies were unable to show a clear association between fatigue and hemoglobin levels. Recently, new insights were afforded by the implementation of innovative survey instruments that assess the effects of fatigue and other (nonfatigue) symptoms of anemia on the patients well-being and quality of life. The use of these validated instruments has shown a direct effect of hemoglobin levels on fatigue and other quality of life parameters. Thus, amelioration of anemia and fatigue should be considered a primary endpoint of antineoplastic and supportive-care treatment of cancer patients. Accordingly, the search for new simplified methods of assessment of fatigue and other anemia-related symptoms and their treatment outcomes should be strongly encouraged.

Geography of clinical cancer research publications from 1995 to 1999.

In this paper, we study the geography of publications in clinical cancer research from 1995 to 1999. A Medline search was performed to retrieve papers in clinical oncology reporting phase I, II and III studies published between 1995 and 1999. Only studies reporting antiblastic chemotherapy have been considered, either alone or in combination with other treatments. For each country, the total number of papers, the total Impact Factor (IF), and the mean IF were determined. Similar calculations were performed to compare the European Union versus North America. 3142 papers were identified. The United States ranks first by number of papers (37.7% share), followed by Italy (9.8%), the United Kingdom (8.5%) and Japan (6.9%). Investigators at European institutions published a higher number of papers compared with their North American colleagues (1362 versus 1288). Still the mean IF of North American papers is higher than the papers with a European address (3.54 versus 3.14). The majority of phase I studies were performed in North America, while most of phase III studies were performed in Europe. These results provide information on the geography of clinical cancer research worldwide, which may reflect the human and economic resources involved in this field.

Increased blood volume and CD34+CD38- progenitor cell recovery using a novel umbilical cord blood collection system

A major problem with the use of umbilical cord/placental blood (UCB) is the limited blood volume that can be collected from a single donor. In this study, we evaluated a novel system for the collection of UCB and analyzed the kinetics of output of hematopoietic stem cells in the collected blood.

Dramatic tumour response to pemetrexed single-agent in an elderly patient with malignant peritoneal mesothelioma: a case report

BackgroundTo date, there is no standard treatment for unresectable malignant peritoneal mesothelioma; either best supportive care or systemic chemotherapy with palliative intent are accepted options.Case presentationHere, we report the case of a 79-year old patient with malignant peritoneal mesothelioma who was treated with pemetrexed single-agent and obtained an impressive long-lasting response.ConclusionSingle-agent pemetrexed is a treatment option for malignant peritoneal mesothelioma in selected elderly patients or in patients with unpaired performance status.

Relevance of Scheduling to the Efficacy of 5-Fluorouracil Alone and in Combination with Other Agents

Until 4–5 years ago the hot topics in clinical colorectal cancer research were scheduling of 5-fluorouracil (5-FU) and its biochemical modulation. The long series of clinical failures on one side and the lack of strong evidence for something new coming up soon, generated the feeling that several years should pass before seeing appreciable progress in the clinical management of this disease. The situation has changed dramatically. Recently, in the last few years, a series of well-designed, well-conducted, randomized studies have demonstrated the value of CPT-11 as second line treatment of patients with advanced colorectal cancer (1,2) and subsequently the value of CPT-11 + 5-FU in the front line treatment of this disease (3–5). Oxaliplatin is somewhat behind CPT-11, but it elicits similar optimism among oncologists, particularly in Europe (6,7). although from a research perspective the small improvements afforded by the two new agents, particularly CPT-11, must be greeted as major breakthroughs, caution must be exercised from a broader perspective. The very small (< 3 mo) advantage in survival for CPT-11 + 5-FU combination vs 5-FU alone must be weighed against the increased toxicity and cost of the combinations. It is thus a pity that most of the research aimed at defining the best 5-FU schedule and modulation has been dropped: first, because the issue whether the new agents are most effective when given in combination or sequentially after 5-FU failure is still not solved; second, because it is likely that each of the new agents produces different effects depending on the schedule of 5-FU used when given in combination.

Impact of low-dose computed tomography screening on lung cancer mortality among asbestos-exposed workers

Background We previously showed that low-dose computed tomography (LDCT) screening in asbestos-exposed workers is effective in detecting lung cancer (LC) at an early stage. Here, we evaluate whether LDCT screening could reduce mortality from LC in such a high-risk population. Methods Within a cohort of 2433 asbestos-exposed men enrolled in an Occupational Health surveillance programme, we compared mortality between the participants in the ATOM002 study (LDCT-P, N  =  926) and contemporary non-participants (LDCT-NP, N  =  1507). We estimated standardized mortality ratios for the LDCT-P and LDCT-NP populations using regional and national rates (SMR_FVG and SMR_ITA, respectively). We compared survival for all causes, all neoplasms, LC and malignant neoplasm of pleura (MNP) between LDCT-P and LDCT-NP using Cox proportional hazard models adjusted for age, smoking history, asbestos exposure level and comorbidities. Results A reduction in mortality from LC was observed in the LDCT-P group compared with regional and national figures (SMR_FVG  =  0.55, 95% confidence interval (CI) 0.24-1.09; SMR_ITA  =  0.51, 95% CI 0.22-1.01); this was not the case for the LDCT-NP group (SMR_FVG  =  2.07, 95% CI 1.53-2.73; SMR_ITA  =  1.98, 95% CI 1.47-2.61). A strong reduction in LC mortality was observed for the LDCT-P compared with the LDCT-NP [hazard ratio (HR)  =  0.41, 95% CI 0.17-0.96]. Mortality was also reduced for all causes (HR  =  0.61, 95% CI 0.44-0.84), but not for all neoplasms (HR  =  0.97, 95% CI 0.62-1.50) and MNP (HR  =  0.86, 95% CI 0.31-2.41) within the LDCT-P population. Conclusions In our cohort, participation in the LDCT screening study was associated with reduced mortality from LC. This finding supports the use of LDCT in surveillance programmes for asbestos-exposed workers.

Randomized phase III PITCAP trial and meta-analysis of induction chemotherapy followed by thoracic irradiation with or without concurrent taxane-based chemotherapy in locally advanced NSCLC

BACKGROUND Chemo-radiotherapy is standard of care in the treatment of unresectable stage III NSCLC. We aimed at assessing whether the addition of concurrent taxane-chemotherapy to thoracic irradiation following chemotherapy was able to improve treatment outcome. MATERIAL AND METHODS In PITCAP trial, patients with unresectable stage III NSCLC were randomized to receive 2 cycles of platinum-paclitaxel followed by 60-61.2Gy thoracic irradiation (control arm) or by same radiotherapy with concomitant weekly paclitaxel (experimental arm). A literature-based meta-analysis including all studies with same design was also performed. RESULTS At the time of the second interim analysis, when 151 patients were randomized, accrual was terminated. With a median follow-up of 6.1 years, median survival was 13.2 vs 15.1 months, with a 3-year survival rate of 19.5 vs 21.2% in the control and experimental arm, respectively (HR: 0.97; 95% CI 0.69-1.36; p=0.845). Treatment toxicity was manageable in both arms. The meta-analysis of 5 trials (n=866) confirmed the lack of a meaningful effect on 1-year overall survival of a taxane added concurrently to radiotherapy. CONCLUSIONS These results do not support a meaningful survival benefit with the addition of single agent taxane given concurrently to radiotherapy after platinum-based induction in locally advanced NSCLC.

Lung cancer and mesothelioma screening with low-dose spiral computed tomography (LDCT) in 1,000 asbestos-exposed workers: An Alpe-Adria Thoracic Oncology Multidisciplinary group study (ATOM 002)

7048 Background: LDCT is more sensitive than chest radiography (CXR) for detection of early stage lung cancer in heavy smokers. However, little is known about LDCT screening in asbestos-exposed subjects. To address this issue, we have designed a prospective, nonrandomized trial to evaluate baseline and annual repeat screening with LDCT in 1,000 asymptomatic asbestos-exposed workers. Here, we report the results of the baseline screening. METHODS Eligibility criteria include: exposure to asbestos, age 40 to 75 yrs, no prior cancer or severe concomitant conditions, no chest CT scan in the last 2 yrs. After written informed consent, eligible subjects undergo a structured interview, CXR and LDCT. Subjects with negative baseline exams undergo annual repeat LDCT. Subjects with positive baseline exams undergo high resolution CT (HRCT) and additional diagnostic workup. RESULTS Between February 2002 and October 2003, 1007 volunteers have been enrolled. Subject characteristics: median age, 59 yrs; males, 97%; smoking history, 66%; former or current shipyard workers, 78%; median asbestos exposure time, 30 yrs. The following data refer to 943 participants. On LDCT, 619 non calcified nodules (NCN) have been identified in 41% of participants. CXR detected 43 nodules. Pleural abnormalities have been detected in 42% and 69% of participants by CXR and LDCT, respectively. So far, six cases of stage I lung cancer have been diagnosed and treated with radical surgery: 3 bronchioloalveolar carcinomas, 1 carcinosarcoma, 2 adenocarcinomas. In addition, one malignant pleural mesothelioma and one thymic carcinoid have been identified. CONCLUSIONS LDCT seems to be useful for the early detection of lung cancer also in asbestos-exposed subjects. Annual repeat LDCT screening may provide information on the natural history and evolution of asbestos-related pleural abnormalities. Study supported by Compagnia di San Paolo, Torino, and Provincia di Gorizia. No significant financial relationships to disclose.