Publications by authors named "Marc Maynadie"

146 Publications

Trends in endocrine therapy prescription and survival in patients with non-metastatic hormone receptor positive breast cancer treated with endocrine therapy: A population based-study.

Breast 2021 Jun 11;59:79-86. Epub 2021 Jun 11.

Côte d'Or Breast and Gynecological Cancer Registry, Epidemiology and Quality of Life Research Unit, INSERM U1231, Georges Francois Leclerc Centre - UNICANCER, Dijon, France; National Quality of Life and Cancer Platform, Dijon, France.

Purpose: To identify prognostic factors of invasive-disease free survival (iDFS) in women with non-metastatic hormone receptor positive (HR+) breast cancer (BC) in daily routine practice.

Methods: We performed a retrospective study using data from the Côte d'Or breast and gynecological cancer registry in France. All women diagnosed with primary invasive non-metastatic HR + BC from 1998 to 2015 and treated by endocrine therapy (ET) were included. Women with bilateral tumors or who received ET for either metastasis or relapse were excluded. We performed adjusted survival analysis and Cox regression to identify prognostic factors of iDFS.

Results: A total of 3976 women were included. Age at diagnosis, ET class, SBR grade, treatment, stage and comorbidity were independently associated with iDFS. Women who had neither surgery nor radiotherapy had the highest risk of recurrence (HR = 3.75, 95%CI [2.65-5.32], p < 0.0001). Receiving aromatase inhibitors (AI) was associated with a lower risk of recurrence (HR = 0.70, 95%CI [0.54-0.90], p = 0.055) compared to tamoxifen. Compared to women with no comorbidities, women with 1 or 2 comorbidities were more likely to receive AI (OR = 1.63, 95%CI [1.22-2.17], p = 0.0009).

Conclusions: Comorbidities, age at diagnosis and previous treatment were associated with iDFS in non-metastatic HR + BC patients. This study also showed that women who received tamoxifen for their cancer experienced worse iDFS compared to women treated with AI.
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http://dx.doi.org/10.1016/j.breast.2021.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242053PMC
June 2021

Flexible Modeling of Net Survival and Cure by AML Subtype and Age: A French Population-Based Study from FRANCIM.

J Clin Med 2021 Apr 13;10(8). Epub 2021 Apr 13.

Dijon-Bourgogne University Hospital, Registre Bourguignon des Cancers Digestifs, F-21000 Dijon, France.

With improvements in acute myeloid leukemia (AML) diagnosis and treatment, more patients are surviving for longer periods. A French population of 9453 AML patients aged ≥15 years diagnosed from 1995 to 2015 was studied to quantify the proportion cured (P), time to cure (TTC) and median survival of patients who are not cured (MedS). Net survival (NS) was estimated using a flexible model adjusted for age and sex in sixteen AML subtypes. When cure assumption was acceptable, the flexible cure model was used to estimate P, TTC and MedS for the uncured patients. The 5-year NS varied from 68% to 9% in men and from 77% to 11% in women in acute promyelocytic leukemia (AML-APL) and in therapy-related AML (t-AML), respectively. Major age-differenced survival was observed for patients with a diagnosis of AML with recurrent cytogenetic abnormalities. A poorer survival in younger patients was found in t-AML and AML with minimal differentiation. An atypical survival profile was found for acute myelomonocytic leukemia and AML without maturation in both sexes and for AML not otherwise specified (only for men) according to age, with a better prognosis for middle-aged compared to younger patients. Sex disparity regarding survival was observed in younger patients with t-AML diagnosed at 25 years of age (+28% at 5 years in men compared to women) and in AML with minimal differentiation (+23% at 5 years in women compared to men). All AML subtypes included an age group for which the assumption of cure was acceptable, although P varied from 90% in younger women with AML-APL to 3% in older men with acute monoblastic and monocytic leukemia. Increased P was associated with shorter TTC. A sizeable proportion of AML patients do not achieve cure, and MedS for these did not exceed 23 months. We identify AML subsets where cure assumption is negative, thus pointing to priority areas for future research efforts.
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http://dx.doi.org/10.3390/jcm10081657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069423PMC
April 2021

Hematological Malignancies in Giant Cell Arteritis: a French population-based study.

Rheumatology (Oxford) 2021 Apr 1. Epub 2021 Apr 1.

Department of Internal Medicine and Clinical Immunology, Dijon University Hospital, Dijon, France.

Objectives: An increased risk of hematological malignancies (HM) has been reported in giant cell arteritis (GCA) patients. Our study aimed to investigate the incidence and the type of HM occurring in GCA.

Methods: All patients with GCA and HM living in Côte D'Or (France) were identified by crossing data from the RHEMCO (Registre des Hémopathies Malignes de Côte d'Or) and those having a positive temporal artery biopsy between 1st January 2001 and 31 December 2018.

Results: Among 276 biopsy-proven GCA patients, 14 HM were identified in 12 patients (4.3%). In comparison with the general population aged over 50 years, the incidence of myeloid HM and myeloproliferative syndromes were increased in GCA patients (standardized incidence ratios = 2.71 and 5.16, respectively), with a specific increase in men with GCA (SIR = 4.82 and 9.04, respectively) but not in women. In addition, the study of standardized incidence ratios depending on the chronology between GCA and HM diagnoses suggests that there was an increased risk of developing GCA in men but not in women, after a diagnosis of myeloid HM (SIR = 9.56), especially if it was a MPS (SIR = 17.56).

Conclusions: Our study shows a particular epidemiology of HM in GCA patients, which is characterized by an increased incidence of myeloid HM, especially MPS, in male GCA patients. The chronology of the diagnoses of GCA and HM raises the hypothesis that clonal hematopoiesis may be implicated in some cases of GCA.
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http://dx.doi.org/10.1093/rheumatology/keab328DOI Listing
April 2021

Identification of novel, clonally stable, somatic mutations targeting transcription factors PAX5 and NKX2-3, the epigenetic regulator LRIF1, and BRAF in a case of atypical B-cell chronic lymphocytic leukemia harboring a t(14;18)(q32;q21).

Cold Spring Harb Mol Case Stud 2021 02 19;7(1). Epub 2021 Feb 19.

University of Burgundy-ISITE-BFC-Institut national de la santé et de la recherche médicale (Inserm) UMR1231, Faculty of Medicine, 21079 Dijon, France.

Diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) is usually straightforward, involving clinical, immunophenotypic (Matutes score), and (immuno)genetic analyses (to refine patient prognosis for treatment). CLL cases with atypical presentation (e.g., Matutes ≤ 3) are also encountered, and for these diseases, biology and prognostic impact are less clear. Here we report the genomic characterization of a case of atypical B-CLL in a 70-yr-old male patient; B-CLL cells showed a Matutes score of 3, chromosomal translocation t(14;18)(q32;q21) (), mutated , deletion 17p, and mutations in , (subclonal), and (subclonal). Quite strikingly, a novel mutation that was predicted to be loss of function was also seen. Exome sequencing identified, in addition, a potentially actionable mutation, together with novel somatic mutations affecting the homeobox transcription factor , known to control B-lymphocyte development and homing, and the epigenetic regulator , which is implicated in chromatin compaction and gene silencing. Neither nor mutations, predicted to be loss of function, have previously been reported in B-CLL. Sequencing confirmed the presence of these mutations together with , , and mutations, with the t(14;18)(q32;q21) translocation, in the initial diagnostic sample obtained 12 yr prior. This is suggestive of a role for these novel mutations in B-CLL initiation and stable clonal evolution, including upon treatment withdrawal. This case extends the spectrum of atypical B-CLL with t(14;18)(q32;q21) and highlights the value of more global precision genomics for patient follow-up and treatment in these patients.
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http://dx.doi.org/10.1101/mcs.a005934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903887PMC
February 2021

Occupational exposure to organic dust and risk of lymphoma subtypes in the EPILYMPH case-control study.

Scand J Work Environ Health 2021 Jan 25;47(1):42-51. Epub 2020 Sep 25.

Department of Medical Sciences and Public Health, Occupational Medicine unit, University of Cagliari, Monserrato (Cagliari) Italy.

Objectives This study aimed to estimate the risk of lymphoma and its major subtypes in relation to occupational exposure to specific organic dusts. Methods We explored the association in 1853 cases and 1997 controls who participated in the EpiLymph case-control study, conducted in six European countries in 1998-2004. Based on expert assessment of lifetime occupational exposures, we calculated the risk of the major lymphoma subtypes associated with exposure to six specific organic dusts, namely, flour, hardwood, softwood, natural textile, synthetic textile, and leather, and two generic (any types) groups: wood and textile dusts. Risk was predicted with unconditional regression modeling, adjusted by age, gender, study center, and education. Results We observed a 2.1-fold increase in risk of follicular lymphoma associated with ever exposure to leather dust [95% confidence interval (CI) 1.01-4.20]. After excluding subjects who ever worked in a farm or had ever been exposed to solvents, risk of B-cell lymphoma was elevated in relation to ever exposure to leather dust [odd ratio (OR) 2.2, 95% CI 1.00-4.78], but it was not supported by increasing trends with the exposure metrics. Risk of Hodgkin lymphoma was elevated (OR 2.0, 95% CI 0.95-4.30) for exposure to textile dust, with consistent upward trends by cumulative exposure and three independent exposure metrics combined (P=0.023, and P=0.0068, respectively). Conclusions Future, larger studies might provide further insights into the nature of the association we observed between exposure to textile dust and risk of Hodgkin lymphoma.
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http://dx.doi.org/10.5271/sjweh.3925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801142PMC
January 2021

Association of ionizing radiation dose from common medical diagnostic procedures and lymphoma risk in the Epilymph case-control study.

PLoS One 2020 10;15(7):e0235658. Epub 2020 Jul 10.

CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

Medical diagnostic X-rays are an important source of ionizing radiation (IR) exposure in the general population; however, it is unclear if the resulting low patient doses increase lymphoma risk. We examined the association between lifetime medical diagnostic X-ray dose and lymphoma risk, taking into account potential confounding factors, including medical history. The international Epilymph study (conducted in the Czech-Republic, France, Germany, Ireland, Italy, and Spain) collected self-reported information on common diagnostic X-ray procedures from 2,362 lymphoma cases and 2,465 frequency-matched (age, sex, country) controls. Individual lifetime cumulative bone marrow (BM) dose was estimated using time period-based dose estimates for different procedures and body parts. The association between categories of BM dose and lymphoma risk was examined using unconditional logistic regression models adjusting for matching factors, socioeconomic variables, and the presence of underlying medical conditions (atopic, autoimmune, infectious diseases, osteoarthritis, having had a sick childhood, and family history of lymphoma) as potential confounders of the association. Cumulative BM dose was low (median 2.25 mGy) and was not positively associated with lymphoma risk. Odds ratios (ORs) were consistently less than 1.0 in all dose categories compared to the reference category (less than 1 mGy). Results were similar after adjustment for potential confounding factors, when using different exposure scenarios, and in analyses by lymphoma subtype and by type of control (hospital-, population-based). Overall no increased risk of lymphoma was observed. The reduced ORs may be related to unmeasured confounding or other sources of systematic bias.We found little evidence that chronic medical conditions confound lymphoma risk and medical radiation associations.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0235658PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351167PMC
September 2020

Occupational exposure to ionizing radiation and risk of lymphoma subtypes: results of the Epilymph European case-control study.

Environ Health 2020 04 25;19(1):43. Epub 2020 Apr 25.

Department of Medical Sciences and Public Health, University of Cagliari, SS554, km 4.500, 09042, Monserrato (Cagliari), Italy.

Background: Evidence linking risk of lymphoma and B-cell lymphoma subtypes to ionizing radiation is inconclusive, particularly at low exposure levels.

Methods: We investigated risk of lymphoma (all subtypes), B-cell lymphomas, and its major subtypes, associated with low-level occupational exposure to ionizing radiation, in 2346 lymphoma cases and 2463 controls, who participated in the multicenter EpiLymph case-control study. We developed a job-exposure matrix to estimate exposure to ionizing radiation, distinguishing between internal and external radiation, and we applied it to the lifetime occupational history of study subjects, We calculated the Odds Ratio (OR) and its 95% confidence interval (95% CI) for lymphoma (all subtypes combined), B-cell lymphoma, and its major subtypes using unconditional, polytomous logistic regression adjusting for age, gender, and education.

Results: We did not observe an association between exposure metrics of external and internal radiation and risk of lymphoma (all subtypes), nor with B-cell lymphoma, or its major subtypes, at the levels regularly experienced in occupational settings. An elevated risk of diffuse large B cell lymphoma was observed among the most likely exposed study subjects with relatively higher exposure intensity, which would be worth further investigation.

Conclusions: Further investigation is warranted on risk of B cell lymphoma subtypes associated with low-level occupational exposure to external ionizing radiation, and to clarify whether lymphoma should be included among the cancer outcomes related to ionizing radiation.
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http://dx.doi.org/10.1186/s12940-020-00596-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7183712PMC
April 2020

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Front Oncol 2019 28;9:1539. Epub 2020 Jan 28.

Interdisciplinary Department of Medicine, University of Bari, Bari, Italy.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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http://dx.doi.org/10.3389/fonc.2019.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999122PMC
January 2020

How should we diagnose and treat blastic plasmacytoid dendritic cell neoplasm patients?

Blood Adv 2019 12;3(24):4238-4251

Laboratoire d'Hématologie, CHU Estaing 1, Clermont-Ferrand, France.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive leukemia for which we developed a nationwide network to collect data from new cases diagnosed in France. In a retrospective, observational study of 86 patients (2000-2013), we described clinical and biological data focusing on morphologies and immunophenotype. We found expression of markers associated with plasmacytoid dendritic cell origin (HLA-DRhigh, CD303+, CD304+, and cTCL1+) plus CD4 and CD56 and frequent expression of isolated markers from the myeloid, B-, and T-lymphoid lineages, whereas specific markers (myeloperoxidase, CD14, cCD3, CD19, and cCD22) were not expressed. Fifty-one percent of cytogenetic abnormalities impact chromosomes 13, 12, 9, and 15. Myelemia was associated with an adverse prognosis. We categorized chemotherapeutic regimens into 5 groups: acute myeloid leukemia (AML)-like, acute lymphoid leukemia (ALL)-like, lymphoma (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP])-like, high-dose methotrexate with asparaginase (Aspa-MTX) chemotherapies, and not otherwise specified (NOS) treatments. Thirty patients received allogeneic hematopoietic cell transplantation (allo-HCT), and 4 patients received autologous hematopoietic cell transplantation. There was no difference in survival between patients receiving AML-like, ALL-like, or Aspa-MTX regimens; survival was longer in patients who received AML-like, ALL-like, or Aspa-MTX regimens than in those who received CHOP-like regimens or NOS. Eleven patients are in persistent complete remission after allo-HCT with a median survival of 49 months vs 8 for other patients. Our series confirms a high response rate with a lower toxicity profile with the Aspa-MTX regimen, offering the best chance of access to hematopoietic cell transplantation and a possible cure.
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http://dx.doi.org/10.1182/bloodadvances.2019000647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929390PMC
December 2019

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Genet Epidemiol 2019 10 13;43(7):844-863. Epub 2019 Aug 13.

Medicina Traslazionale, Università del Piemonte Orientale, Vercelli, Italy.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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http://dx.doi.org/10.1002/gepi.22242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763347PMC
October 2019

Gastric MALT lymphoma in a population-based study in France: clinical features, treatments and survival.

Aliment Pharmacol Ther 2019 09 26;50(6):654-663. Epub 2019 Jul 26.

Strasbourg, France.

Background: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a rare disease, and most available data on gastric MALT lymphoma (GML) come from clinical studies of selected patients treated in centres of excellence.

Aims: To analyse the clinical features, management and survival of GML patients in a population-based study in France METHODS: All new cases of GML diagnosed between 2002 and 2010 in 11 French areas covered by cancer registries were included. Pathology reports were verified and, if necessary, reviewed by an expert pathologist. All clinical data were retrospectively collected from medical files and analysed using stata V. 14 software.

Results: Four hundred and sixteen patients with confirmed GML (50% male, median age 67 years) were identified. Among them, 44 showed an early transformation into diffuse large B cell lymphoma and were considered to have had an initially missed high-grade lymphoma. At diagnosis, 76% of patients were at stage IE/II, and 24% at stage III/IV of the disease. Helicobacter pylori infection was found in 57% of the patients. Eradication treatment was administered to 76% of patients and complete remission (CR) was obtained in 39%. One hundred and ninety patients received at least one other treatment, including 10 already in CR after eradication. Altogether, CR was obtained in 70% of patients and the 5-year overall survival was 79% (95% CI [75-83]).

Conclusions: In comparison to clinical series, in the general population, GMLs are more frequently diagnosed at an advanced stage, their clinical management is heterogeneous, and there is a risk of misdiagnosis and overtreatment. These results highlight the necessity of following currently available guidelines in this field.
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http://dx.doi.org/10.1111/apt.15409DOI Listing
September 2019

Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia.

Nat Commun 2018 10 10;9(1):4182. Epub 2018 Oct 10.

Epidemiology Research Program, American Cancer Society, Atlanta, 30303, GA, USA.

Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40-31.03, P = 1.36 × 10) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45-6.96, P = 8.75 × 10). Both risk alleles are observed at a low frequency among controls (~2-3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.
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http://dx.doi.org/10.1038/s41467-018-06541-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6180091PMC
October 2018

HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes.

Cancer Res 2018 07 7;78(14):4086-4096. Epub 2018 May 7.

Department of Public Health, Clinical and Molecular Medicine, University of Cagliari, Cagliari, Italy.

A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of "heterozygote advantage" regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06-1.60; OR MZL = 1.45, 95% CI = 1.12-1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24-3.55; OR MZL = 2.10, 95% CI = 0.99-4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci ( trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. HLA gene diversity reduces risk for non-Hodgkin lymphoma. .
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http://dx.doi.org/10.1158/0008-5472.CAN-17-2900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6065509PMC
July 2018

Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis.

Blood 2018 06 19;131(23):2541-2551. Epub 2018 Apr 19.

Huntsman Cancer Institute and Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT.

Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; = 4.4 × 10). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; = 7.8 × 10) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; = 9.8 × 10). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.
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http://dx.doi.org/10.1182/blood-2017-11-814608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992865PMC
June 2018

Prognostic value of multicenter flow cytometry harmonized assessment of minimal residual disease in acute myeloblastic leukemia.

Hematol Oncol 2018 Apr 7;36(2):422-428. Epub 2017 Dec 7.

Hematology Biology, University Hospital, Nantes, France.

The assessment of minimal residual disease (MRD) in acute myeloblastic leukemia is of growing interest as a prognostic marker of patients' outcome. Multiparameter flow cytometry (MFC), tracking leukemia-associated immunophenotypic patterns, has been shown in several studies to be a useful tool to investigate MRD. Here, we report a multicenter prospective study which allowed to define a harmonized analysis strategy, as well as the efficacy of MFC MRD to predict outcome. This study included 276 patients, in 10 different MFC centers, of whom 268 had at least 1 MRD check point. The combination of a CD45, CD34, and CD33 backbone, with the addition of CD117, CD13, CD7, and CD15 in 2 five-color tubes allowed to define each patient's multiparameter immunophenotypic characteristics at diagnosis, according to a Boolean combination of gates. The same individual diagnosis gating strategy was then applied at each MRD time point for each patient. MRD levels were stratified according to log by log thresholds, from 5 × 10 (the classical morphological threshold to define remission) down to <5 × 10 . MRD was found to be constantly negative (<5 × 10 ) for 148 patients. Survival analyses significantly associated MRD negativity with a good prognosis and any positive value with poorer outcome. All P values were <0.0001 both for disease-free and overall survival at the earliest time point (post-induction, MRD1) as well as when considering all time points together. Finally, MRD levels were independent of cytogenetics and allowed in fact to further stratify all cytogenetics risk groups. In summary, this multicenter study demonstrates that a simple combination of immunophenotypic markers successfully allows for the detection of MRD in acute myeloblastic leukemia patients, with a strong correlation to outcome.
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http://dx.doi.org/10.1002/hon.2488DOI Listing
April 2018

Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma.

Lupus Sci Med 2017 12;4(1):e000187. Epub 2017 Nov 12.

Department of Health Sciences, University of York, York, UK.

Objective: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL.

Methods: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis.

Results: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765.

Conclusions: These data suggest several plausible genetic links between DLBCL and SLE.
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http://dx.doi.org/10.1136/lupus-2016-000187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5715504PMC
November 2017

Survival benefit of mantle cell lymphoma patients enrolled in clinical trials; a joint study from the LYSA group and French cancer registries.

J Cancer Res Clin Oncol 2018 Apr 11;144(4):629-635. Epub 2017 Oct 11.

Registre des hémopathies malignes de Côte d'Or, Faculté des Sciences de Santé, Inserm UMR 1231, Université de Bourgogne F-Comté, 7 Bd Jeanne d'Arc, 21079, Dijon Cedex, France.

Purpose: Mantle cell lymphoma (MCL) is a rare non-Hodgkin's lymphoma entity with a poor prognosis. Therapeutic advances have improved the survival of patients enrolled in clinical trials; however, their impact on patients outside clinical trials remains unclear. In this work, we compared patient outcome inside and outside clinical trials.

Methods: We identified MCL patients recorded in six French population-based registries between 2008 and 2012 to perform a comparison with patients enrolled in two prospective multicenter MCL clinical trials conducted by the LYSA group during the same period. Variables associated with inclusion in a clinical trial were identified using a logistic regression. Pohar-Perme estimator and Nelson et al. flexible parametric model was used to estimate net survival probabilities and prognosis factors on excess mortality.

Results: A total of 312 registry patients were compared to the 372 patients enrolled in LYSA clinical trials. Patients included in clinical trials were younger (median age 60 vs 74, p < 0.001). Age and Ann Arbor stage IV were independently associated with enrollment [OR = 0.09 (0.06-0.12) and OR = 1.61 (1.11-2.34), respectively]. The 4 year net survival was better in clinical trials [79.9% (75.9-84.7) vs 60.3% (53.6-67.0)]. This result was confirmed in multivariate analysis in patients older than 65 years with a lower excess mortality rate [0.33 (0.17-0.66)].

Conclusions: MCL included in trials are highly selected patients who are not representative of MCL patients who are encountered in everyday practice. With widened inclusion criteria, clinical trial patients could be more representative of the general population.
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http://dx.doi.org/10.1007/s00432-017-2529-9DOI Listing
April 2018

Impact of Expert Pathologic Review of Lymphoma Diagnosis: Study of Patients From the French Lymphopath Network.

J Clin Oncol 2017 Jun 1;35(18):2008-2017. Epub 2017 May 1.

Camille Laurent, Nadia Amara, Georges Delsol, and Pierre Brousset, Institut Universitaire du Cancer-Oncopole de Toulouse; Centre Hospitalier Universitaire (CHU) Toulouse; Camille Laurent, Georges Delsol, and Pierre Brousset, Institut National de la Santé et de la Recherche Médicale (INSERM), U.1037, Centre de Recherche en Cancerologie de Toulouse-Purpan, Laboratoire d'Excellence Toulouse Cancer; Thomas Filleron, Institut Claudius Regaud, L'Institut Universitaire du Cancer de Toulouse, Toulouse; Marine Baron, Corinne Haioun, Christiane Copie-Bergman, and Philippe Gaulard, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Henri Mondor-Albert Chenevier; Corinne Haioun, Christiane Copie-Bergman, and Philippe Gaulard, INSERM U955, Université Paris-Est, Créteil; Mylène Dandoit, Marc Maynadié, and Laurent Martin, CHU de Dijon, Dijon; Marie Parrens, Beatrice Vergier, and Antoine de Mascarel, Hôpital du Haut Lévêque, CHU de Bordeaux, Bordeaux; Bettina Fabiani, AP-HP, Hôpital Saint-Antoine; Nicole Brousse and Thierry Jo Molina, AP-HP, Hôpital Necker; Josette Brière, AP-HP, Hôpital Saint Louis; Fréderic Charlotte, AP-HP, Hôpital Pitié Salpétrière; Diane Damotte, AP-HP, Hôpitaux Universitaires Paris Centre, Paris; Alexandra Traverse-Glehen and Françoise Berger, CHU Lyon-Sud; Catherine Chassagne-Clement, Centre Léon Bérard, Lyon; Marie-Christine Copin, Univ Lille, CHU Lille, Lille; Patrick Tas, CHU de Rennes, Rennes; Marie-Christine Rousselet, CHU d'Angers, Angers; Thérèse Rousset, Hôpital Gui de Chauliac, CHU de Montpellier, Montpellier; Luc Xerri, Aix-Marseille Univ, Institut Paoli-Calmettes, Marseille; Anne Moreau and Céline Bossard, Hôpital Hôtel Dieu, CHU de Nantes, Nantes; Antoine Martin, Hôpital Avicenne, Bobigny, Bobigny; Peggy Dartigues, Institut Gustave Roussy, Villejuif; Isabelle Soubeyran, Institut Bergonié, Bordeaux; Michel Peoch, CHU de Saint Etienne, Saint Etienne; Pierre Dechelotte, CHU de Clermont-Ferrand, Clermont-Ferrand; Jean-François Michiels, CHU de Nice, Nice; Flavie Arbion, CHU de Tours, Tours; Isabelle Quintin-Roué, CHU de Brest, Brest; Jean-Michel Picquenot, Centre Henri Becquerel, CHU de Rouen, Rouen; Martine Patey, CHU de Reims, Reims; Blandine Fabre, CHU de Grenoble, Grenoble; Henri Sevestre, CHU d'Amiens, Amiens; Cécile Le Naoures, CHU de Caen, Caen; Marie-Pierre Chenard-Neu, CHU de Strasbourg, Strasbourg; Claire Bastien, CHU de Nancy, Nancy; Sylvie Thiebault, CH de Mulhouse, Mulhouse; Manuela Delage, CHU de Limoges, Limoges; Gilles Salles, Hospices Civils de Lyon, CHU Lyon-Sud; Gilles Salles, INSERM1052, Centre National de la Recherche Scientifique 5286, Université Claude Bernard, Pierre Bénite, France; Tony Petrella, Pathology University of Montréal, Hôpital Maisonneuve-Rosemont, Montréal, Canada.

Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.
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http://dx.doi.org/10.1200/JCO.2016.71.2083DOI Listing
June 2017

A 5-color flow cytometric method for extended 8-part leukocyte differential.

Cytometry B Clin Cytom 2017 11 5;92(6):498-507. Epub 2017 Apr 5.

Service d'Hématologie Biologique, CHU de Dijon, Dijon, France.

Objectives: Microscopic leukocyte differentials display many drawbacks. Several single 5 to 8-color tubes using multiparameter flow cytometry (MFC) are able to provide extended differentials with sequential gating-based analysis strategies. We investigated a new 5-color MFC method to perform an extended 8-part differential with a simplified gating strategy.

Methods: Whole blood was stained with a combination of antibodies including HLA-DR-FITC/CD19-PE/CD45-ECD/CD16-PC5 + CD71-PC5/CD5-PC7.

Results: An original approach was developed to exclude debris and straightforwardly gate the cells to identify sixteen populations. Strong correlations were obtained with the analyzer for neutrophils, lymphocytes, monocytes, and eosinophils (R >0.9). Abnormal cells, such as immature granulocytes and blast cells were identified with a good sensitivity and excellent correlation against cytomorphologic review (R =0.66 and 0.99, respectively). The choice of HLA-DR and CD5 improved specificity for the identification of activated T-lymphocytes and some lymphoid neoplastic cells, respectively.

Conclusions: Here a new cytometric differential is proposed with a robust gating strategy which may be used even by unskilled cytometrists and can be easily automated. © 2017 International Clinical Cytometry Society.
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http://dx.doi.org/10.1002/cyto.b.21524DOI Listing
November 2017

Relapsed chronic lymphocytic leukemia retreated with rituximab: interim results of the PERLE study.

Leuk Lymphoma 2017 06 9;58(6):1366-1375. Epub 2017 Feb 9.

q Hématologie, CHU Robert Debré , Reims , France.

This prospective non-interventional study assessed the management of relapsed/refractory CLL after one or two treatments with rituximab, and retreatment with a rituximab-based regimen. An interim analysis was performed at the end of the induction period in 192 evaluable patients. Median age was 72 years [35-89], first relapse (55%), and second relapse (45%). Rituximab administered during first (68%), second (92%), or both treatment lines (20%). R-bendamustine administered in 56% of patients, R-purine analogs (21%), and R-alkylating agents (19%). The overall response rate (ORR) was 74.6%, in favor of R-purine analogs (90%), R-bendamustine (75%), and R-alkylating agents (69%). Lower ORR in Del 17p patients (43%) and third time rituximab (31%). Most frequent adverse events were hematological (23% patients) including neutropenia (11%) and infections (12%); grade 3/4 AEs (23% patients), mainly hematological (18%); death during induction treatment (7%). This first large study focusing on relapsed/refractory CLL patients retreated with rituximab-based regimens is still ongoing.
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http://dx.doi.org/10.1080/10428194.2016.1243673DOI Listing
June 2017

Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC).

Cancer Epidemiol Biomarkers Prev 2017 06 21;26(6):876-885. Epub 2017 Feb 21.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville, Maryland.

Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case-control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI. We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls. In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04-1.14; = 0.007]. We observed significant heterogeneity by study design ( = 0.04), noting the BMI-multiple myeloma association only for population-based studies ( = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m; OR, 1.2; 95% CI, 1.1-1.3; = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI ( <0.0001); we noted statistically significant associations with multiple myeloma for persons overweight (25-<30 kg/m) or obese (30+ kg/m) in both younger and usual adulthood (vs. individuals consistently <25 kg/m), but not for those overweight or obese at only one time period. BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood. These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. .
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http://dx.doi.org/10.1158/1055-9965.EPI-16-0762-TDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5457306PMC
June 2017

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia.

Nat Commun 2017 02 6;8:14175. Epub 2017 Feb 6.

Department of Haematology, Royal Victoria Infirmary, Newcastle upon Tyne NE1 4LP, UK.

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10), 1q42.13 (rs41271473, P=1.06 × 10), 4q24 (rs71597109, P=1.37 × 10), 4q35.1 (rs57214277, P=3.69 × 10), 6p21.31 (rs3800461, P=1.97 × 10), 11q23.2 (rs61904987, P=2.64 × 10), 18q21.1 (rs1036935, P=3.27 × 10), 19p13.3 (rs7254272, P=4.67 × 10) and 22q13.33 (rs140522, P=2.70 × 10). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.
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http://dx.doi.org/10.1038/ncomms14175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5303820PMC
February 2017

Factors related to the relative survival of patients with diffuse large B-cell lymphoma in a population-based study in France: does socio-economic status have a role?

Haematologica 2017 03 1;102(3):584-592. Epub 2016 Dec 1.

Registre des Hémopathies Malignes de la Gironde, Institut Bergonie, Bordeaux, France.

The survival of patients with diffuse large B-cell lymphoma has increased during the last decade as a result of addition of anti-CD20 to anthracycline-based chemotherapy. Although the trend is encouraging, there are persistent differences in survival within and between the USA and European countries suggesting that non-biological factors play a role. Our aim was to investigate the influence of such factors on relative survival of patients with diffuse large B-cell lymphoma. We conducted a retrospective, multicenter, registry-based study in France on 1165 incident cases of diffuse large B-cell lymphoma between 2002 and 2008. Relative survival analyses were performed and missing data were controlled with the multiple imputation method. In a multivariate analysis, adjusted for age, sex and International Prognostic Index, we confirmed that time period was associated with a better 5-year relative survival. The registry area, the medical specialty of the care department (onco-hematology other), the time to travel to the nearest teaching hospital, the place of treatment (teaching not-teaching hospital -borderline significance), a comorbidity burden and marital status were independently associated with the 5-year relative survival. Adjusted for first-course treatment, inclusion in a clinical trial and treatment discussion in a multidisciplinary meeting were strongly associated with a better survival outcome. In contrast, socio-economic status (determined using the European Deprivation Index) was not associated with outcome. Despite therapeutic advances, various non-biological factors affected the relative survival of patients with diffuse large B-cell lymphoma. The notion of lymphoma-specific expertise seems to be essential to achieve optimal care management and reopens the debate regarding centralization of these patients' care in hematology/oncology departments.
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http://dx.doi.org/10.3324/haematol.2016.152918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394966PMC
March 2017

Subcutaneous Panniculitis-like T-cell Lymphoma: Immunosuppressive Drugs Induce Better Response than Polychemotherapy.

Acta Derm Venereol 2017 Mar;97(3):358-364

Service d'anatomie pathologique, Hôpital Necker-Enfants Malades, Paris, APHP, Université Paris Descartes, Sorbonne Paris Cité, France.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare condition usually considered to have a favourable prognosis. However, it is not known whether polychemotherapy or immunosuppressive-based therapy is the best approach for treating SPTCL. Using data collected between 2000 and 2012 in France, we analysed clinical, biological and pathological data of 27 patients with SPTCL. Medical history revealed that 40% of patients had been previously diagnosed with an autoimmune disorder and 22% with inflammatory panniculitis. Haemophagocytic syndrome was present in 37% of cases. Autoantibodies were positive in 65% of cases. Complete remission (CR) was reached in 74% of cases. Immunosuppressive drug treatment was given in 69.5% of patients (group 1) and polychemotherapy in 30.5% (group 2). CR was 81.2% and 28.5% (p?=?0.025), respectively. Progression rate was 6.2% and 42.8% (p?=?0.067), respectively. This study suggests that immunosuppressive drugs should be considered as the first-line treatment for SPTCL.
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http://dx.doi.org/10.2340/00015555-2543DOI Listing
March 2017

Pancreatic cancer: Wait times from presentation to treatment and survival in a population-based study.

Int J Cancer 2016 09 14;139(5):1073-80. Epub 2016 May 14.

CHU Dijon Bourgogne, Registre Bourguignon des Cancers Digestifs, F-21000 Dijon, France; INSERM, LNC UMR866, F-21000 Dijon, France; Université Bourgogne Franche-Comté, LNC UMR866, F-21000 Dijon, France.

Pancreatic survival is one of the worst in oncology. To what extent wait times affect outcomes in unknown No population-based study has previously explored patient and treatment delays among individuals with pancreatic cancer. The aim of this study was to estimate patient and treatment delays in patients with pancreatic cancer and to measure their association with survival in a nonselected population. All patients diagnosed with pancreatic cancer for the first time between 2009 and 2011 and registered in two French digestive cancer registries were included. Patient delay (time from onset of symptoms until the first consultation categorized into <1 or ≥1 month), and treatment delay (time between the first consultation and treatment categorized into less or more than 29 days, the median time) were collected. Overall delay was used to test associations between survival and the timeliness of care by combining patient delay and treatment delay. Patient delay was longer than 1 month in 46% of patients. A patient delay longer than one month was associated with the absence of jaundice (p < 0.001) and the presence of metastasis (p = 0.003). After adjusting for other covariates, such as symptoms and treatment, the presence of metastasis was negatively associated with treatment delay longer than 29 days (p = 0.025). After adjustment for other covariates, especially metastatic dissemination and the result of the resection, overall delay was not significantly associated with prognosis. We found little evidence to suggest that timely care was associated with the survival of patients.
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http://dx.doi.org/10.1002/ijc.30166DOI Listing
September 2016

Genetically predicted longer telomere length is associated with increased risk of B-cell lymphoma subtypes.

Hum Mol Genet 2016 Apr 9;25(8):1663-76. Epub 2016 Feb 9.

Centre for Big Data Research in Health, University of New South Wales, Sydney, NSW, Australia.

Evidence from a small number of studies suggests that longer telomere length measured in peripheral leukocytes is associated with an increased risk of non-Hodgkin lymphoma (NHL). However, these studies may be biased by reverse causation, confounded by unmeasured environmental exposures and might miss time points for which prospective telomere measurement would best reveal a relationship between telomere length and NHL risk. We performed an analysis of genetically inferred telomere length and NHL risk in a study of 10 102 NHL cases of the four most common B-cell histologic types and 9562 controls using a genetic risk score (GRS) comprising nine telomere length-associated single-nucleotide polymorphisms. This approach uses existing genotype data and estimates telomere length by weighing the number of telomere length-associated variant alleles an individual carries with the published change in kb of telomere length. The analysis of the telomere length GRS resulted in an association between longer telomere length and increased NHL risk [four B-cell histologic types combined; odds ratio (OR) = 1.49, 95% CI 1.22-1.82,P-value = 8.5 × 10(-5)]. Subtype-specific analyses indicated that chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) was the principal NHL subtype contributing to this association (OR = 2.60, 95% CI 1.93-3.51,P-value = 4.0 × 10(-10)). Significant interactions were observed across strata of sex for CLL/SLL and marginal zone lymphoma subtypes as well as age for the follicular lymphoma subtype. Our results indicate that a genetic background that favors longer telomere length may increase NHL risk, particularly risk of CLL/SLL, and are consistent with earlier studies relating longer telomere length with increased NHL risk.
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http://dx.doi.org/10.1093/hmg/ddw027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854019PMC
April 2016