malignant lymphoma is a heterogeneous group of diseases with a wide spectrum of histological subtypes .
traditionally , malignant lymphomas have been divided into hodgkin lymphomas and non - hodgkin lymphomas .
more than 40 subgroups are defined ; both indolent and aggressive variants exist , and a wide range of treatment is used . the danish national lymphoma registry ( lyfo )
was established in 1982 , covering the western part of denmark ( jutland and funen ) , including patients with non - hodgkin lymphoma . in 1998 ,
the lyfo aims to register the clinical and paraclinical characteristics of patients diagnosed with malignant lymphoma in denmark .
the lyfo aims to monitor the clinical course of the disease as well as to monitor and improve the quality of treatment nationwide by benchmarking departments and patient risk groups .
the lyfo includes all patients diagnosed with malignant lymphoma in denmark , referred to one of the ten departments of hematology .
patients with cutaneous lymphomas , some hiv+-associated lymphomas , and some lymphomas where treatment is futile are not referred to hematological departments and hence not registered in the lyfo .
patients diagnosed and treated outside of denmark are not registered ; according to the database registration , it is two patients per year .
patients who relapse where the initial lymphoma diagnosis was prior to start of the registry in that region are not registered . by the end of 2014 , ~23,000 patients were registered since 1982 .
since it is a national quality database , all departments of hematology are obligated to register patients in the lyfo at the time of diagnosis , at the end of first - line treatment , at relapse , and at the end of follow - up or death .
standardized forms are used to collect data on lymphoma patients ( table 1 ) . since 2005
, the registration is submitted electronically through a secure internet - based database system , and all information is saved electronically . for each patient , four forms are available in a consecutive manner ( figure 1 ) . at the time of diagnosis
the department responsible for the treatment initiation and evaluation has the obligation to enter the form .
the diagnosis is coded according to the who classification of tumours of haematopoietic and lymphoid tissues.1 since a minor subset has a discordant diagnose , this is also registered .
ann arbor stage , b - symptoms , largest tumor diameter , eastern cooperative oncology group performance status , concomitant neoplastic diseases , and treatment strategy are required in the form .
in addition to a number of laboratory test results ( table 1 ) , information of each nodal and extranodal involvement sites is required .
the treatment form consists of detailed information on the first - line treatment : chemotherapy regimens , treatment with monoclonal antibodies , radiotherapy , radioimmunotherapy , major surgery , and date and type of eventually autologous stem - cell therapy .
a response assessment is required and has been adjusted to the different versions of the international response criteria for malignant lymphoma.2 furthermore , toxicity assessment is recorded for patients experiencing toxicity grades iii and iv.3 in the case of clinical or histologically confirmed relapse or refractory disease , defined as progression within 3 months after termination of first - line treatment , a relapse form is requested .
this form is also completed for all patients who were initially observed without need of treatment .
the relapse form requires date of relapse , lymphoma histology at relapse , treatment information of second - line treatment , and response assessment identical to the treatment form .
a follow - up form is requested at death or termination of outpatient follow - up .
this form includes information on vital status , date of follow - up or death , and disease remission status .
the four schemes in the database are merged to an analyzable dataset , where new data fields are derived from the entered values in the schemes .
this process utilizes calculation of a number of prognostic indexes such as the international prognostic index ( ipi)4 and the follicular lymphoma international prognostic index5 and a number of nodal and extranodal sites , in addition to calculation of both result and process quality indicators .
result quality indicators are mortality 30 and 180 days after diagnosis for patients receiving treatment , response to first - line treatment and kaplan - meier survival estimates 1 , 3 , and 5 years after the time of diagnosis .
the process quality indicators include time from diagnosis to start of treatment , fulfillment of entered data used in the international prognostic index , and the inclusion rate in clinical trials . to ensure high registry completeness , the lyfo is cross - referenced with the danish national patient registry and the national pathology registry .
since all patients with a hospital admission , both as inpatient and outpatient , are registered in the danish national patient registry with diagnosis and date of contact , all patients referred to a hematological department are identified by this cross - reference.6 departments can instantly retrieve lists of patients with missing registration in the database , both at time of diagnosis and time of an eventual relapse .
all departments register in the lyfo and fulfill the demand of coverage of at least 90% .
the department responsible for the treatment initiation and evaluation has the obligation to enter the form .
the diagnosis is coded according to the who classification of tumours of haematopoietic and lymphoid tissues.1 since a minor subset has a discordant diagnose , this is also registered .
ann arbor stage , b - symptoms , largest tumor diameter , eastern cooperative oncology group performance status , concomitant neoplastic diseases , and treatment strategy are required in the form .
in addition to a number of laboratory test results ( table 1 ) , information of each nodal and extranodal involvement sites is required .
the treatment form consists of detailed information on the first - line treatment : chemotherapy regimens , treatment with monoclonal antibodies , radiotherapy , radioimmunotherapy , major surgery , and date and type of eventually autologous stem - cell therapy .
a response assessment is required and has been adjusted to the different versions of the international response criteria for malignant lymphoma.2 furthermore , toxicity assessment is recorded for patients experiencing toxicity grades iii and iv.3
in the case of clinical or histologically confirmed relapse or refractory disease , defined as progression within 3 months after termination of first - line treatment , a relapse form is requested .
this form is also completed for all patients who were initially observed without need of treatment .
the relapse form requires date of relapse , lymphoma histology at relapse , treatment information of second - line treatment , and response assessment identical to the treatment form .
a follow - up form is requested at death or termination of outpatient follow - up .
this form includes information on vital status , date of follow - up or death , and disease remission status .
the four schemes in the database are merged to an analyzable dataset , where new data fields are derived from the entered values in the schemes .
this process utilizes calculation of a number of prognostic indexes such as the international prognostic index ( ipi)4 and the follicular lymphoma international prognostic index5 and a number of nodal and extranodal sites , in addition to calculation of both result and process quality indicators .
result quality indicators are mortality 30 and 180 days after diagnosis for patients receiving treatment , response to first - line treatment and kaplan - meier survival estimates 1 , 3 , and 5 years after the time of diagnosis .
the process quality indicators include time from diagnosis to start of treatment , fulfillment of entered data used in the international prognostic index , and the inclusion rate in clinical trials . to ensure high registry completeness , the lyfo is cross - referenced with the danish national patient registry and the national pathology registry .
since all patients with a hospital admission , both as inpatient and outpatient , are registered in the danish national patient registry with diagnosis and date of contact , all patients referred to a hematological department are identified by this cross - reference.6 departments can instantly retrieve lists of patients with missing registration in the database , both at time of diagnosis and time of an eventual relapse .
all departments register in the lyfo and fulfill the demand of coverage of at least 90% .
in addition to the follow - up form , which is completed at the time of termination of outpatient follow - up or death , whichever occurs first , a linkage to the danish civil registration system secures that date of death is available.7 thereby , no patient is lost to follow - up .
data from the lyfo has for decades been used for both clinical epidemiological research and for monitoring the treatment of lymphoma patients in denmark.8 the danish lymphoma group , who runs the database , publishes annually a report based on data from the lyfo in collaboration with registry support center of epidemiology and biostatistics ( east).9 the quality indicators are presented for each department by year together with comments from clinicians and epidemiologists .
the reports have shown improved 180 days mortality for patients with diffuse large b - cell lymphoma ( dlbcl ) , improving from 12% to 10% during the past 4 years .
the annual report is publically available and is used by both clinicians and for administrative purposes . in case of one department having significant worse outcome than the others , the administrative staff will examine the numbers and differences and draw the clinicians attention to the differences in order to standardize treatment and outcome .
as an example , the survival for patients with dlbcl was significantly lower in two out of ten departments in 20012007
. the survival has increased , but is now at the same level for all departments due to publication of the survival results ( figure 2 ) .
a substantial number of papers originated from the lyfo have been published in the past decade in international journals , and collaboration with other national databases has resulted in unique publications.913 in 2014 , a publication of mantle cell lymphoma showed male sex to be an independent negative prognostic factor , and that both rituximab and autologous stem - cell transplant were independently associated with better outcome.11 a study on routine imaging in the follow - up setting after treatment for dlbcl compared the widespread use of routine imaging in denmark with the more restrictive use in sweden .
no impact was found on survival , and the study concludes that routine imaging for dlbcl in the first complete remission is not recommended.13 data quality in the lyfo has recently been measured through a validation process , and the data quality and coverage was found to be very high with positive predictive values for individual variables ranging from 87% to 100% using individual medical records as reference and a registration completeness of 94.9% using danish national patient registry ( dnpr ) as reference.14,15
health care professionals ( eg , medical doctors , study nurses ) report to the database , and consent is not required from patients due to the danish legislation .
registration in the lyfo is approved by the national board of health and the danish data protection agency ( 2006 - 54 - 2093 ) .
a data entry manual is publically available , and training is performed locally . prior to submission of a form , an internal validation of the data fields is performed and the clinician has to clarify open issues ( eg , date of diagnosis , lymphoma subtype ) before submission of the form can be performed .
funding from the danish regions allows the maintenance and development of the database and the database office .
registry support center of epidemiology and biostatistics east is responsible for it support as well as statistical and epidemiological support .
the lyfo is a nationwide registry , established in 1982 , with extensive information on all lymphoma patients treated at a department of hematology in denmark .
the database is used for quality assurance , clinical epidemiological research , and administrative purposes .
 aim of databasethe danish national lymphoma registry ( lyfo ) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in denmark.study populationthe lyfo database was established in 1982 as a seminational database including all lymphoma patients referred to the departments of hematology . 
 the database became nationwide on january 1 , 2000.main variablesthe main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation . up to four forms are completed for each patient : a primary registration form , a treatment form , a relapse form , and a follow - up form . 
 variables are used to calculate six result quality indicators ( mortality 30 and 180 days after diagnosis , response to first - line treatment , and survival estimates 1 , 3 , and 5 years after the time of diagnosis ) , and three process quality indicators ( time from diagnosis until the start of treatment , the presence of relevant diagnostic markers , and inclusion rate in clinical protocols).descriptive dataapproximately 23,000 patients were registered in the period 19822014 with a median age of 65 years ( range : 16100 years ) and a male / female ratio of 1.23:1 . 
 patients can be registered with any of 42 different subtypes according to the world health organization classifications.conclusionlyfo is a nationwide database for all lymphoma patients in denmark and includes detailed information . 
 this information is used for both epidemiological research and clinical follow - up as well as for administrative purposes . 
Aim of database
Study population
Main variables
Primary registration form
Treatment form
Relapse form
Follow-up form
Follow-up
Examples of research
Administrative issues and funding
Conclusion