CD200 genotype is associated with clinical outcome of patients with multiple myeloma.

Immune dysfunction in patients with MM affects both the innate and adaptive immune system. Molecules involved in the immune response pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of immune checkpoint molecules in predicting the myeloma control and immunological scape as mechanism of disease progression. We retrospectively analyzed the clinical impact of the CD200 genotype (rs1131199 and rs2272022) in 291 patients with newly diagnosed MM. Patients with a CD200 rs1131199 GG genotype showed a median overall survival (OS) significantly lower than those with CC+CG genotype (67.8 months versus 94.4 months respectively; p: 0.022) maintaining significance in the multivariate analysis. This effect was specially detected in patients not receiving an autologous stem cell transplant (auto-SCT) (p < 0.001). In these patients the rs1131199 GG genotype negatively influenced in the mortality not related with the progression of MM (p: 0.02) mainly due to infections events.

Genetic variants of CTLA4 are associated with clinical outcome of patients with multiple myeloma.

Immune dysfunction in patients with multiple myeloma (MM) affects both the innate and adaptive immune system. Molecules involved in the immune checkpoint pathways are essential to determine the ability of cancer cells to escape from the immune system surveillance. However, few data are available concerning the role of these molecules in predicting the kinetics of progression of MM. We retrospectively analysed polymorphisms of CTLA4 (rs231775 and rs733618), BTLA (rs9288953), CD28 (rs3116496), PD-1 (rs36084323 and rs11568821) and LAG-3 (rs870849) genes in 239 patients with newly diagnosed MM. Patients with a CTLA4 rs231775 AA/AG genotype showed a median progression-free survival (PFS) significantly lower than those with GG genotype (32.3 months versus 96.8 months respectively; p: 0.008). The 5-year PFS rate was 25% for patients with grouped AA and AG genotype vs 55.4% for patients with GG genotype. Multivariate analysis confirmed the CTLA4 rs231775 genotype as an independent risk factor for PFS (Hazard Ratio (HR): 2.05; 95% CI: 1.0-6.2; p: 0.047). Our results suggest that the CTLA4 genotype may identify patients with earlier progression of MM. This polymorphism could potentially be used as a prognostic biomarker.

Time trends and survival of marginal zone lymphoma over 25 years in Girona, Spain (1994-2018).

OBJECTIVE: To analyze the incidence, incidence trends, and survival of marginal zone lymphomas (MZLs) in Girona and to describe these indicators based on the location in the case of extranodal MZLs. METHODS: Population-based study of MZL collected in the Girona Cancer Registry, 1994-2018. Sociodemographic data, tumor location, and stage were obtained from clinical records. Crude (CR) and age-adjusted (ASRE ) incidence rates expressed per 100,000 person-years (p-y) were calculated. Joinpoint regression models were used for the trend analysis according to the MZL group. Five-year observed and net survival were analyzed. RESULTS: A total of 472 MZLs were included, 44 (9.3%) were nodal, 288 (61.0%) extranodal, 122 (25.9%) splenic, and the rest (n = 18) MZL, NOS. The CR for the MZL was 2.89 × 100,000 p-y (95% CI: 2.63-3.15), the ASRE was 3.26 × 100,000 p-y (95% CI: 2.97-3.57), and the annual percentage change (APC) was 1.6 (95% CI: 0.5-2.7). The ASRE for nodal MZL was 0.30 × 100,000 p-y (95% CI: 0.22-0.41) and showed an APC of 2.9% (95% CI: -16.4-26.6). For extranodal MZL, the ASRE was 1.98 × 100,000 p-y (95% CI: 1.76-2.23) and the APC was -0.4 (95% CI: -2.0-1.2). The most frequent locations of this type of MZL were the gastric (35.4%), skin (13.2%), and respiratory system (11.8%). The ASRE of the splenic MZL was 0.85 (95% CI: 0.71-1.02) with an APC of 12.8 (95% CI: 2.5-24.0). The 5-year net survival of MZL was 82.1% (95% CI: 76.3-86.5). CONCLUSIONS: This study reveals differences in the incidence and trend of the incidence of MZL according to the subgroup, showing a significant increase in the overall MZL mainly due to splenic MZL type.

Population-based analysis of the prevalence of BRAF mutation in patients diagnosed with cutaneous melanoma and its significance as a prognostic factor.

The prevalence of BRAF mutation has been reported in between 38% and 48% of melanoma patients, based on mainly Stage III or metastatic melanoma, however, information based on population-based studies is scarce. We performed a population-based retrospective cohort study to determine the prevalence of the BRAF mutation in patients diagnosed with in situ and infiltrating cutaneous malignant melanoma in the province of Girona between 2009 and 2011. Using the database of the Girona Cancer Registry, we performed BRAF mutation analysis based on paraffin-embedded tissue. This data was then correlated with other known clinical and histological prognostic factors for survival. We found 286 incident cases of cutaneous melanoma in the Girona Cancer Registry database. Excluding missing cases, BRAF-mutated patients constituted 38.9% of "in situ" melanoma cases and 53.8% of invasive melanoma cases. Five-year relative survival was not statistically different between BRAF-mutated patients (93.6%; 95% CI: 87.1-100.5) and non-mutated patients (84.3%, 95% CI: 75.3-94.8). Only stage was significant as a prognostic factor for survival based on multivariate analysis. From our population-based study, we conclude that BRAF mutation is not an independent prognostic factor for melanoma survival.

Challenges in assessing the real incidence of chronic lymphocytic leukemia: 16 years of epidemiological data from the province of Girona, Spain.

Determining chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) incidence is challenging for two reasons: cancer registries tend to underreport CLL cases and its diagnostic criteria changed markedly in 2008. No studies have reported incidence rates dealing with both difficulties, and thus CLL/SLL burden in Europe is currently uncertain. Herein, we present accurate CLL/SLL incidence in a Spanish region during 1998-2013, using the population-based Girona Cancer Registry (GCR). We detected an 18.2% under-reporting of CLL/SLL cases when combining records from the GCR and additional information sources (i.e., records of flow cytometry laboratories, hospital registries and hematologists' databases). In addition, age-adjusted rates (using the 2013 European population) changed from 7.57 (95% CI 6.87; 8.30) in 1998-2008 to 6.35 (95% CI 5.51; 7.30) in 2009-2013. Overall, completeness of CLL/SLL data requires accurate diagnosis and reporting of cases. Revision of cancer registry operations to include CLL/SLL-specific surveillance is likely to ensure that the monitoring of this malignancy is entirely accurate.

Incidence and survival of Hodgkin lymphoma patients in Girona (Spain) over three decades: a population-based study.

Hodgkin lymphoma (HL) is characterized by heterogeneous histologic findings, clinical presentation and outcomes. Using the Girona population-based cancer registry data we sought to explore the incidence of HL over three decades in Girona Province (Spain) and examine the relationship between clinical features at diagnosis and survival. From 1985 to 2013, 459 cases were recorded. Patients were stratified by sex, age group, stage at diagnosis, histological subtypes and the presence of B-symptoms. The crude incidence rate (CR) was 2.7 and the corresponding European age-adjusted rate was 2.6, being higher in men than in women (sex ratio=1.6). Incidence remained constant throughout the period of study. Nodular sclerosis was the most frequent histology and showed an increasing incidence over time [estimated annual percentage change=+2.4, 95% confidence interval (CI): 0.8-4.0]. The 5-year observed survival and relative survival of patients diagnosed with HL were 73.1% (95% CI: 69.0-77.5) and 74.6% (95% CI: 70.0-79.4), respectively. No statistical differences in observed survival were observed across the three decades of study (P=0.455). Clinical parameters negatively influencing 5-year relative survival in the multivariate analysis were as follows: age at diagnosis at least 65 years; clinical stage IV; and presence of B-symptoms. These current patterns of presentation and outcomes of HL help delineate key populations in order to explore risk factors for HL and strategies to improve treatment outcomes.

Survival variations by country and age for lymphoid and myeloid malignancies in Europe 2000-2007: Results of EUROCARE-5 population-based study.

BACKGROUND: Significant advances in the management of patients with lymphoid and myeloid malignancies entered clinical practice in the early 2000's. The EUROCARE-5 study database provides an opportunity to assess the impact of these changes at the population level by country in Europe. We provide survival estimates for clinically relevant haematological malignancies (HM), using the International Classification of Diseases for Oncology 3, by country, gender and age in Europe. METHODS: We estimated age-standardised relative survival using the complete cohort approach for 625,000 adult patients diagnosed in 2000-2007 and followed up to 2008. Survival information was provided by 89 participating cancer registries from 29 European countries. Mean survival in Europe was calculated as the population weighted average of country-specific estimates. RESULTS: On average in Europe, 5-year relative survival was highest for Hodgkin lymphoma (81%; 40,625 cases), poorest for acute myeloid leukaemia (17%; 57,026 cases), and intermediate for non-Hodgkin lymphoma (59%; 329,204 cases), chronic myeloid leukaemia (53%; 17,713 cases) and plasma cell neoplasms (39%; 94,024 cases). Survival was generally lower in Eastern Europe and highest in Central and Northern Europe. Wider between country differences (>10%) were observed for malignancies that benefited from therapeutic advances, such as chronic myeloid leukaemia, chronic lymphocytic leukaemia, follicular lymphoma, diffuse large B-cell lymphoma and multiple myeloma. Lower differences (<10%) were observed for Hodgkin lymphoma. CONCLUSIONS: Delayed or reduced access to innovative and appropriate therapies could plausibly have contributed to the observed geographical disparities between European regions and countries. Population based survival by morphological sub-type is important for measuring outcomes of HM management. To better inform quality of care research, the collection of detailed clinical information at the population level should be prioritised.

Is survival in myeloid malignancies really improving? A retrospective 15-year population-based study.

Myeloid malignancies (MMs) are heterogeneous groups of diseases which present different prognoses. Using data from the population-based Girona Cancer Registry, we estimated the relative survival (RS) rates and relative excess risk of death among patients with MMs in the province of Girona between 1994 and 2008. The 5-year RS rate was 49.7%, ranging from 20.2% for acute myeloid leukemia (AML) to 75.3% for myeloproliferative neoplasms (MPN). Marked differences in RS were observed when the age of patients was considered: an increase in RS was mainly found in younger patients with myelodysplastic syndromes and MPN. Furthermore, cases of chronic myeloid leukemia treated with imatinib had a significantly better outcome compared with those that were untreated. Despite the slight improvement in the survival rate of younger patients with AML, RS remained stable for 15 years, as no significant improvements were made in the management of the disease during that period.

Proporción de cáncer de mama en mujeres de 50 a 69 años de Girona según el método de detección / Proportion of breast cancer in women aged 50 to 69 years from Girona, Spain, according to detection method

Fundamento y objetivo: El objetivo de este estudio fue determinar el estadio tumoral, la proporción de casos y la tasa específica por edad de las pacientes con cáncer de mama (CM) según el método de detección. Material y método: Los datos se obtuvieron del Registro de Cáncer de Girona de base poblacional. Se incluyeron las mujeres de 50 a 69 años diagnosticadas de CM en la provincia de Girona durante el período 1999-2006 (n = 1.254). Se clasificaron los CM según el método de detección: cáncer de cribado, cáncer de intervalo y otros. Se calculó la proporción de casos y la tasa específica por edad según el método de detección.Resultados: Durante los años 2002-2006, un 42,2% de los CM diagnosticados en Girona fueron cánceres de cribado, el 52,0% se detectaron fuera del Programa de Detección Precoz del Cáncer de Mama (PDPCM), y el 5,8% fueron cánceres de intervalo. Con la implementación del PDPCM disminuyó la incidencia del CM diagnosticado fuera del programa, aumentó la de los cánceres de cribado y poco después incrementó la de los cánceres de intervalo. Conclusiones: Durante los primeros años del funcionamiento del PDPCM (2002-2006) los casos de cáncer de intervalo representaron un porcentaje bajo (5,8%) respecto el total de CM diagnosticados en mujeres de 50 a 69 años en la provincia de Girona (AU)

Background and objective: The aim of this study was to determine the tumor stage, the proportion of cases and the age specific rate of breast cancer (BC) cases according to detection method. Material and method: Cases of women aged 50 to 69 years diagnosed with BC in the Girona province during 1999-2006 were extracted from the population-based Girona Cancer Registry (n = 1,254). BC was classified by detection method: screen-detected cancer, interval cancer and others. Proportion of cases and age-specific incidence were calculated according to detection method. Results: During the period 2002-2006, the proportion of screen-detected cancers, interval cancers and other cancers were 42.2%, 5.8% and 52.2%, respectively. After implementation of the early detection of breast cancer program (PDPCM), the incidence of screen-detected cases raised; thereafter, interval cancers also increased and the rate of other cancers decreased. Conclusions: In the Girona province during the fully implemented PDPCM period (2002-2006), interval cancers represented a low proportion (5.8%) of women diagnosed with BC at 50 to 69 years old (AU)

Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study.

BACKGROUND: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. METHODS: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997-99, 2000-02, 2003-05, 2006-08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. FINDINGS: We analysed 560 444 cases. From 1997-99 to 2006-08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7-43·4] to 55·4% [54·6-56·2], p<0·0001), follicular lymphoma (58·9% [57·3-60·6] to 74·3% [72·9-75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6-33·9] to 54·4% [52·5-56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7-56·2] to 61·9% [57·0-66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1-76·0] to 79·3% [78·4-80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1-67·1] to 69·0% [68·1-69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0-30·6] to 39·6% [38·8-40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7-32·0] to 41·1% [39·0-43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9-13·3] to 14·8% [14·2-15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7-71·8] to 74·9% [73·8-75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. INTERPRETATION: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival. FUNDING: Compagnia di San Paolo, Fondazione Cariplo, European Commission, and Italian Ministry of Health.

[Proportion of breast cancer in women aged 50 to 69 years from Girona, Spain, according to detection method]. / Proporción de cáncer de mama en mujeres de 50 a 69 años de Girona según el método de detección.

BACKGROUND AND OBJECTIVE: The aim of this study was to determine the tumor stage, the proportion of cases and the age specific rate of breast cancer (BC) cases according to detection method. MATERIAL AND METHOD: Cases of women aged 50 to 69 years diagnosed with BC in the Girona province during 1999-2006 were extracted from the population-based Girona Cancer Registry (n=1,254). BC was classified by detection method: screen-detected cancer, interval cancer and others. Proportion of cases and age-specific incidence were calculated according to detection method. RESULTS: During the period 2002-2006, the proportion of screen-detected cancers, interval cancers and other cancers were 42.2%, 5.8% and 52.2%, respectively. After implementation of the early detection of breast cancer program (PDPCM), the incidence of screen-detected cases raised; thereafter, interval cancers also increased and the rate of other cancers decreased. CONCLUSIONS: In the Girona province during the fully implemented PDPCM period (2002-2006), interval cancers represented a low proportion (5.8%) of women diagnosed with BC at 50 to 69 years old.

Incidence and survival of chronic myelomonocytic leukemia in Girona (Spain): a population-based study, 1993-2007.

Chronic myelomonocytic leukemia is a very rare blood cancer observed mostly in the elderly. Here we report the incidence trends and survival of patients with chronic myelomonocytic leukemia over a 15-year period (1993-2007). Cases were provided by the population-based Girona Cancer Registry. The crude incidence rate was 0.72/100,000 inhabitants/year. No statistically significant increase in trends was detected over the 15 years. Median overall survival was 28 months although survival markedly decreased with advancing age. The 5-years observed and relative survivals were 20% and 29%, respectively. This is the first population-based study that reports the incidence and survival of chronic myelomonocytic leukemia in Spain.