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Purpose: This study sought to ascertain whether there might be an association between radon concentrations and age, gender, histologic type, and tumor stage at diagnosis., Materials and Methods: Lung cancer cases from different multicenter case-control studies were analyzed, and clinical data were retrieved from electronic health records and personal interviews. A radon device was placed in all dwellings of participants, and we then tested the existence of an association between residential radon and lung cancer characteristics at diagnosis., Results: Of the total of 829 lung cancer cases included, 56.7% were smokers or ex-smokers. There was no association between indoor radon concentrations and age, gender, histologic type or tumor stage at diagnosis. Median indoor radon concentrations increased with age at diagnosis for men, but not for women. When analyzing participants exposed to more than 1000 Bq/m 3 , a predominance of small cell lung cancer and a higher presence of advanced stages (IIIB and IV) were observed., Conclusions: There seems to be no association between radon and age, gender, histologic type or tumor stage at diagnosis. Higher radon exposure is more frequent in the case of small-cell lung cancer.

Introduction : Lung cancer is the most important cause of cancer mortality. It is a multifactorial disease with multiple risk factors, including residential radon exposure. Areas covered : The aim of this paper was to review the epidemiology of residential radon exposure and its impact on lung cancer risk. While tobacco is the main risk factor of lung cancer, residential radon is the first cause in never-smokers and the second in ever-smokers. Moreover, the synergistic effect between tobacco consumption and radon exposure should be considered. However, the biological mechanism by which radon and its decay products induce lung cancer is not entirely known. Expert opinion : Residential radon is usually neglected by clinicians. In fact, no lung cancer risk score (predicting incidence or mortality) includes radon as a variable. Further studies are needed to find out the molecular pathways of radon that cause lung cancer and whether this radioactive gas is also involved in the development of other diseases other than lung cancer. There is a clear need to increase awareness among administrations, health professionals and the general population in order to take the necessary measures to reduce this harmful exposure, particularly in radon-prone areas.

Introduction: Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL). Histological transformation (HT) refers to the evolution of a clinically indolent NHL to a clinically aggressive one, defined as those lymphomas in which survival is limited to a few months when untreated. Areas covered: HT is associated with rapid progression of lymphadenopathy, infiltration of extranodal sites, development of systemic symptoms, and elevated serum level of lactate dehydrogenase (LDH). It is frequently related to a poor prognosis, and the median survival after transformation is less than 2 years. Transformation to diffuse large B cell lymphoma (DLBCL) in patients with FL occurs at an annual rate of approximately 3% for the first 15 years, after which the risk of HT falls for reasons that remain unclear. Expert commentary: Although it has long been assumed that transformation reflects the emergence of an aggressive subclone of cells from the primary FL, recent studies suggest that FL transformation might also arise by divergent evolution from a more immature common progenitor cell. Studies on genomic changes and DNA sequencing have shed some light onto the process of transformation. Nowadays, we know that HT is a complex process where several molecular pathways are involved.

The WORLD07 study characterizes lung cancer in Spanish women. This analysis investigated lung cancer features in never-smoking women. Of 2072 women recruited, 2035 were analyzed. Patient characteristics and demographics were similar for current/former smokers and never smokers. Among never smokers, 38.3% were exposed to passive smoking. Non-small-cell lung cancer was the most common type (78.8% of current/former smokers and 96.1% of never smokers) and adenocarcinoma the most common histology (69.1% and 83.4% respectively). There was a high incidence of lung cancer in Spanish never-smoking women and a high proportion (about 50%) had mutant epidermal growth factor receptor.

Classical Hodgkin lymphoma (cHL) is frequently related to Epstein-Barr virus (EBV) infection. Its malignant capacity is attributed to disruption of an EBV-host balance influenced by environmental and genetic drivers. EBV structures activate Type I interferon (IFN) pathway of the innate immunity, therefore, genetic polymorphisms could influence this response. We explored the impact of four single nucleotide polymorphisms (SNPs) on EBV-associated cHL susceptibility. Toll-like receptors 9 (TLR9_rs5743836), and 3 (TLR3_rs3775291), Interleukin-28B (IL28B_rs12979860), and DEAD-box polypeptide 58 (DDX58_rs10813831) were genotyped in 73 EBV-positive and 106 EBV-negative cHL patients and 396 controls. Only DDX58_rs10813831 T-allele was decreased among EBV-positive cHL compared to controls. A stratified analysis in EBV-positive cHL showed that the reduced rate was associated with younger age and nodular sclerosis. In conclusion, DDX58_rs10813831 T-allele may be associated with a reduced risk of nodular sclerosis EBV-related cHL, which suggests a role for RIG-I (retinoic acid-inducible gene I), encoded by DDX58, in these cases.

Purpose: The aim of this study is to assess if there is a relationship between residential radon and lung cancer histological types and patients' age at diagnosis., Materials and Methods: We conducted a multicenter hospital-based case-control study with eight participating hospitals. We included 216 never-smoking cases with primary lung cancer and 329 never-smoking controls. Controls were frequency matched with cases on age and sex distribution. Of them, 198 cases (91.7%) and 275 controls (83.5%) had residential radon measurements., Results: Lung cancer risk reached statistical significance only for adenocarcinoma (Odds ratio [OR] 2.19; 95% Confidence interval [CI] 1.44-3.33), for other histologies the results were marginally significant. Residential radon level was higher for patients diagnosed before 50 and 60 years old than for older lung cancer cases., Conclusions: Residential radon in never smokers seems to be a risk factor for all lung cancer histologies. Individuals diagnosed at a younger age have a higher residential radon concentration, suggesting an accumulative effect on lung cancer appearance.

Hepatitis infection has a high prevalence in patients with non-Hodgkin lymphoma. Our objective was to evaluate clinical characteristics and survival of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) who were hepatitis B and/or C (HBV/HCV) positive. We reviewed 224 patents diagnosed with DLBCL and found 21 to be HBV/HCV positive (9.3%). Significant differences were found in the number of nodal regions affected, four in HBV/HCV positive versus two in virus negative patients, and in liver involvement, which was greater in HBV/HCV positive patients (28.6% vs. 10%, p = 0.028). No significant differences were found in the two groups with respect to the number of relapses or the probability of overall or progression-free survival. Despite the finding of differences with respect to stage, total number of nodal regions affected and liver involvement, HBV/HCV positive and negative patients with DLBCL should receive the same treatment, and the disease responds and evolves equally.

We performed three different studies to obtain additional data on the biological and prognostic role of vascular endothelial growth factor C (VEGFC) in classical Hodgkin lymphoma (cHL): (1) serum VEGFC levels were measured by enzyme-linked immunosorbent assay in 80 patients; (2) immunohistochemical VEGFC expression in tumor tissue was evaluated using a case-control study in 62 patients; (3) gene expression of VEGFC was investigated in vitro in six cHL cell lines, and was compared with expression in inflammatory lymph nodes. Higher serum VEGFC levels were found in patients with cHL than in healthy volunteers (median, 7675 vs. 1358 pg/mL, p < 0.001) and high VEGFC expression in tissue predicted worse progression-free survival at 7 years (41% vs. 91%, p < 0.0001). VEGFC expression in all Hodgkin lymphoma cell lines was higher than the mean expression level in inflammatory lymph nodes. Our data suggest that Hodgkin and Reed-Sternberg cells produce VEGFC, and VEGFC expression could be a novel prognostic factor in cHL.

Relapse is the main cause of therapeutic failure in follicular lymphoma (FL). We set out to evaluate the role of consolidation with Yttrium-90 ibritumomab tiuxetan in patients with intermediate- and high-risk FL after four cycles of CHOP-R (cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab) and two cycles of CHOP. Thirty patients were included. The overall response rate after consolidation therapy was 93%. Of the 18 patients who presented with a partial response after induction treatment, 11 had a complete response after consolidation treatment. The complete clinical response rate was 76.6%. The most important grade 3-4 toxicity was hematological, with 46% thrombopenia and 56% neutropenia. With a median follow-up of 26 months, the means for progression-free survival and overall survival were not reached. Our data support consolidation with Yttrium-90 ibritumomab tiuxetan as an effective treatment, which provides long progression-free and overall survival, in first line after a response to induction treatment in patients with intermediate- and high-risk FL.

Key points and recommendations Follicular lymphoma is a subgroup of non-Hodgkin lymphomas of B-cell origin, characterized by a pattern of remissions and continued relapses. It is the second most common type of lymphoid cancer in Western Europe, representing 22-40% of non-Hodgkin lymphomas. The annual incidence of the disease has increased in recent decades. At this time, and with the arrival of new treatment options, patients' outcomes have significantly improved. It is therefore essential to standardize recommendations for the treatment and follow-up of patients with follicular lymphoma, in each clinical scenario. Searches were performed in Medline (PubMed, 1966-present) and The Cochrane Library, using MeSH (Medical Subject Headings) terms whenever possible. The best scientific evidence was obtained from selected randomized studies and meta-analyses. For recommendations where there was no scientific evidence, the consensus of clinical experts was obtained regarding clinical and therapeutic attitudes to improve the treatment of these patients. Recommendations are compiled according to: (i) induction treatment in first-line; (ii) post-induction treatment in first-line; (iii) rescue treatment after relapse; (iv) post-induction treatment in relapse and (v) subsequent treatments. There are different recommendations for each group. They take into account different variables, such as therapeutic options, patient follow-up, laboratory and imaging data, previous response and special groups. The recommendations contained in this guide have been assigned different grades (A, B, C and D), depending on the level of evidence on which they are based (where there is no scientific evidence, they follow the consensus of Good Clinical Practice: see the Appendix). These guidelines provide healthcare professionals with updated and consensual tools for the better management of patients with follicular lymphoma.

The aim of this study was to determine the prognostic significance of the expression of Lyn, Fyn and Syk in Hodgkin lymphoma and its correlation with Epstein-Barr virus (EBV) infection. With this in mind, 96 patients with classical Hodgkin lymphoma were immunohistochemically evaluated for Lyn, Fyn and Syk expression in Hodgkin and Reed-Sternberg cells, and the results were correlated with the presence of EBV and patient outcomes. These three kinases were heterogeneously expressed in classical Hodgkin lymphoma cases. As there are no cut-offs established for these antibodies, they were introduced as continuous variables in the model. Statistical analysis showed that the expression of Syk and Fyn was significantly associated with shorter failure-free survival. Syk and Fyn may be useful to predict at diagnosis the treatment response of patients with classical Hodgkin lymphoma. There was a significant association between EBV infection and Lyn expression (p < 0.05). Overexpression of Syk and the availability of Syk inhibitors suggest that this molecule might be a therapeutic strategy worthy of development for cases expressing this molecule.

Fewer than half of patients with diffuse large B-cell lymphoma (DLBCL) can be cured. Molecular prognostic factors in the rituximab era must be re-evaluated, because there are few molecular indicators with prognostic value. Samples of DLBCL from 41 newly diagnosed patients with a median follow-up of 52 months were studied. Immunohistochemical staining was performed to investigate the expression of apoptosis-related proteins (Bcl-2 and caspase 3a), cell proliferation (Ki-67), and tumor microenvironmental factors. Two groups were analysed, 23 cases (56%) treated with CHOP and 18 (44%) treated with R-CHOP. Survival analysis showed that cases with overexpression of Bcl-2 had worse overall survival (OS) in the CHOP group. However, OS in the R-CHOP group was adversely affected by lack of caspase 3a staining. In the entire series, cases positive for caspase 3a showed significantly better OS, without significance for other parameters, and caspase 3 was associated with parameters of prognosis and OS in R-CHOP. This is the first study that relates caspase 3a and prognosis in DLBCL.

Survival in Hodgkin lymphoma (HL) has significantly increased, and most relapses occur in the first 2 years. We analyzed the proportion of relapses occurring after 5 years, the method of detection, and survival in the database of patients with HL in our hospital (1967-2005). We undertook a retrospective study of clinical and molecular characteristics with the use of 12 different antibodies (Abs): CD30, CD15, CD20, CD3, BCL-2, BCL-6, CD57, EMA, p53, Ki-67, Aurora kinase A, and PAX-5. We studied 534 patients with HD and found 150 relapses (28%), 30 of which occurred 5 years after the end of treatment. The relapses were detected during a scheduled appointment in 16 (54%) asymptomatic patients. Seven of 30 patients relapsed with a different histological type. There were no statistically significant differences in survival between those patients with a late relapse and new remission and those who never relapsed. None of the molecular markers were associated with relapse. Long-term survival was not significantly different in relapsed patients with remission after treatment compared with patients who never relapsed. We need to maintain active follow-up in order to detect late and recoverable relapses.

We designed a prospective study to measure the left ventricular ejection fraction of 42 patients with non-Hodgkin lymphoma treated with Rituximab-based chemotherapy in a 1-h infusion. Our patients were not selected on the basis of their cardiac status. Cardiac history and other forms of co-morbidity were to be identified on entry. Before treatment, basal left ventricular ejection function (LVEF) was measured and every 6 months after treatment. Most patients were treated with CHOP-Rituximab combinations (79%). A drop in the post-treatment ejection fraction of over 10% from the pre-treatment base figure was found in 13 patients (31% of the total of the series, 39% of those receiving adriamycin-based chemotherapy). None of the patients without adriamycin had a decrease in LVEF. Three patients with drop >10% recovered normally, but when LVEF decreased by over 15%, which occurred in six patients (14.2%), none of them recovered normal level. Patients with normal systolic function had LVEF with a mean of 64.09 (+/-3.86) and patients with decreased systolic function had LVEF with a mean of 59.38 (+/-5.43). Though the data in this study suggest that rapid-infusion Rituximab does not cause relevant cardiac toxicity, there was a high percentage of reductions in LVEF of over 10%.

Hodgkin's disease (HD) is a curable tumoral disease. However, there are groups of patients who suffer relapse and the identification of prognostic factors and the adaptation of treatments to individual risk is one the lines of investigation in this disease. A study was performed on 526 patients diagnosed of HD in our hospital between January 1967 and September 2001. An analysis was made of the most important variables in terms of both disease-free and overall survival. Overall survival in this series of patients was 94% at 2 years, 86% at 5 years, 76% at 10 years and 72% at 15 years. Median survival was 249 months. Factors influencing poor prognosis in the overall survival were: male gender (P < 0.0001), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.0001), B symptoms (P < 0.0001), spleen involvement at diagnosis (P = 0.003), no complete remission after first line treatment (P < 0.0001), and more than 30 years-of-age (P < 0.0001). Disease free survival was 83% at 2 years and 68% at 5 years although without reaching the mean follow-up. The disease free survival study revealed the following risk factors: male gender (P = 0.02), lymphocyte depletion (P < 0.0001), stages III and IV (P < 0.001), B symptoms (P < 0.001), extranodal or splenic involvement (P < 0.05), and no complete remission after first line treatment (P < 0.0001). The result of treatment optimization is that some factors that were considered to indicate a poor prognosis have disappeared, and that others which are useful have appeared and allow us to establish groups with differing risks of relapse and who could be candidates for differentiated treatments.

The treatment of choice for patients with early stage Hodgkin's disease (HD) has been extended field or subtotal nodal irradiation. Remission rates of over 95% have been obtained, however, about 5% of stage I and II patients will suffer from progressive disease while on therapy and an additional 15-20% will relapse. Chemotherapy (Ch) alone has not been adequately tested in early-stage HD. In this study, all HD stage I and II patients treated with Ch alone in the University Hospital "Clínica Puerta de Hierro" between 1980 and 1997 were reviewed. Thirty-five patients were treated between 04/80 and 12/97. All patients achieved complete remission. The median follow-up was 119 months (range 21-240 months), no patients were lost at follow-up. Overall survival (OS) was 97% (IC 95%, 92-100) at 5 years and 88% (IC 95%, 75-100) at 10 years. Failure free survival (FFS) was 93% (IC 95%, 83-100) at 5 years and 66% (IC 95%, 47-86) at 10 years. Three (8.5%) patients died: two due to a second tumour (non-Hodgkin's lymphoma and myeloid acute leukaemia) and the other due to sepsis post-Ch. Univariate and multivariate analysis only associated histology subtype relative risk (RR) 4.0 nodular sclerosis (95% IC, 1.0-5.5; p:0.02) with higher relapse. Other prognostic factors did not reveal significant differences with respect to failure free or OS. In conclusion, we believe that death from HD in early-stage patients is unusual and mortality from causes other than HD occurs many years later. Outside clinical trials due to the lack of clear prognostic factors, with the exception of specific situations, patients should be informed of all the possible alternatives as well as the consequences of the treatments employed. In our experience, it appears that using Ch alone in the initial stages does not jeopardize overall patient survival, with similar results being achieved.

Hodgkin's disease (HD) is a curable disease. However, there are still many questions that remain unanswered in this illness, such as the appearance of unsuspected microscopic active illness a long time after the conclusion of treatment, We do not know of any recent publications that have microscopically studied the presence of unsuspected HD activity in patients who died from causes other than tumoral progression. This aspect was analysed in our series of patients with HD. We studied 486 patients with a median follow-up of 8 years. Autopsy was performed in 40 of 144 non-surviving patients. Active HD was found in 60% (24/40) of the patients at autopsy. Of these, 10 patients (25%, 10/40) with active HD died from causes other than tumoral progression. Six patients had minimal clinically unsuspected isolated tumor foci. In spite of technical advances and the introduction of modern and more aggressive chemotherapy, the discovery of minimal unsuspected residual HD continues in an considerable percentage of patients who die from causes other than tumoral progression.