Population-based information on the survival of patients with myeloid malignancies is rare mainly because some entities were not recognized as malignant until the publication of the third revision of ...the International Classification of Diseases for Oncology and World Health Organization classification in 2000. In this study we report the survival of patients with myeloid malignancies, classified by updated criteria, in Europe. We analyzed 58,800 cases incident between 1995 to 2002 in 48 population-based cancer registries from 20 European countries, classified into HAEMACARE myeloid malignancy groupings. The period approach was used to estimate 5-year relative survival in 2000-2002. The relative overall survival rate was 37%, but varied significantly between the major groups: being 17% for acute myeloid leukemia, 20% for myelodysplastic/myeloproliferative neoplasms, 31% for myelodysplastic syndromes and 63% for myeloproliferative neoplasms. Survival of patients with individual disease entities ranged from 90% for those with essential thrombocythemia to 4% for those with acute myeloid leukemia with multilineage dysplasia. Regional European variations in survival were conspicuous for myeloproliferative neoplasms, with survival rates being lowest in Eastern Europe. This is the first paper to present large-scale, European survival data for patients with myeloid malignancies using prognosis-based groupings of entities defined by the third revision of the International Classification of Diseases for Oncology/World Health Organization classifications. Poor survival in some parts of Europe, particularly for treatable diseases such as chronic myeloid leukemia, is of concern for hematologists and public health authorities.
To assess the risk of secondary nonbreast cancers (SNBCs) in a recently treated population-based cohort of breast cancer patients focused on the association with treatment and prognostic ...implications.
In 58,068 Dutch patients diagnosed with invasive breast cancer between 1989 and 2003, SNBC risk was quantified using standardized incidence ratios (SIRs), cumulative incidence, and Cox regression analysis, adjusted for competing risks.
After a median follow-up of 5.4 years, 2,578 SNBCs had occurred. Compared with the Dutch female population at large, in this cohort, the SIR of SNBCs was increased (SIR, 1.22; 95% CI, 1.17 to 1.27). The absolute excess risk was 13.6 (95% CI, 9.7 to 17.6) per 10,000 person-years. SIRs were elevated for cancers of the esophagus, stomach, colon, rectum, lung, uterus, ovary, kidney, and bladder cancers, and for soft tissue sarcomas (STS), melanoma, non-Hodgkin's lymphoma, and acute myeloid leukemia (AML). The 10-year cumulative incidence of SNBCs was 5.4% (95% CI, 5.1% to 5.7%). Among patients younger than 50 years, radiotherapy was associated with an increased lung cancer risk (hazard ratio HR = 2.31; 95% CI, 1.15 to 4.60) and chemotherapy with decreased risk for all SNBCs (HR = 0.78; 95% CI, 0.63 to 0.98) and for colon and lung cancer. Among patients age 50 years and older, radiotherapy was associated with raised STS risk (HR = 3.43; 95% CI, 1.46 to 8.04); chemotherapy with increased risks of melanoma, uterine cancer, and AML; and hormonal therapy with all SNBCs combined (HR = 1.10; 95% CI, 1.01 to 1.21) and uterine cancer (HR = 1.78; 95% CI, 1.40 to 2.27). An SNBC worsened survival (HR = 3.98; 95%CI 3.77 to 4.20).
Breast cancer patients diagnosed in the 1990 s experienced a small but significant excess risk of developing an SNBC.
To evaluate whether (89)Zr can be used as a PET surrogate label for quantification of (90)Y-ibritumomab tiuxetan ((90)Y-Zevalin) biodistribution and dosimetry before myeloablative radioimmunotherapy.
...Zevalin was labelled with (89)Zr by introducing N-succinyldesferal (N-sucDf) as a second chelate. For comparison of the in vitro stability of (89)Zr-Zevalin and (88)Y-Zevalin (as a substitute for (90)Y), samples were incubated in human serum at 37 degrees C up to 6 days. Biodistribution of (89)Zr-Zevalin and (88)Y-Zevalin was assessed at 24, 48, 72 and 144 h p.i. by co-injection in nude mice bearing the non-Hodgkin's lymphoma (NHL) xenograft line Ramos. The clinical performance of (89)Zr-Zevalin-PET was evaluated via a pilot imaging study in a patient with NHL, who had undergone (18)FFDG-PET 2 weeks previously.
Modification of Zevalin with N-sucDf resulted in an N-sucDf-to-antibody molar ratio of 0.83+/-0.04. After radiolabelling and purification, the radiochemical purity and immunoreactivity of (89)Zr-Zevalin always exceeded 95% and 80%, respectively. (89)Zr-Zevalin showed the same stability in serum as (88)Y-Zevalin, with a radiochemical purity >95% during a period of 6 days. The co-injected (89)Zr-Zevalin and (88)Y-Zevalin conjugates showed a very similar biodistribution, except for liver and bone accumulation at 72 and 144 h p.i., which was significantly higher for (89)Zr than for (88)Y. PET images obtained after injection of (89)Zr-Zevalin showed clear targeting of all known tumour lesions.
(89)Zr-Zevalin and (88)Y-Zevalin showed a very similar biodistribution in mice, implying that (89)Zr-Zevalin-PET might be well suited for prediction of (90)Y-Zevalin biodistribution in a myeloablative setting.
AIM： To analyze, retrospectively in a populationbased study, the management and survival of patients with recurrent rectal cancer initially treated with a macroscopically radical resection obtained ...with total mesorectal excision （TME）.
METHODS： All rectal carcinomas diagnosed during 1998 to 2000 and initially treated with a macroscopically radical resection （632 patients） were selected from the Amsterdam Cancer Registry. For patients with recurrent disease, information on treatment of the recurrence was collected from the medical records.
RESULTS： Local recurrence with or without clinically apparent distant dissemination occurred in 62 patients （10%）. Thirty-two patients had an isolated local recurrence. Ten of these 32 patients （31%） underwent radical re-resection and experienced the highest survival （three quarters survived for at least 3 years）. Eight patients （25%） underwent non-radical surgery （median survival 24 rno）, seven patients （22%） were treated with radio- and/or chemotherapy without surgery （median survival 15 mo） and seven patients （22%） only received best supportive care （median survival 5 too）. Distant dissemination occurred in 124 patients （20%） of whom 30 patients also had a local recurrence. The majority （54%） of these patients were treated with radio- and/or chemotherapy without surgery （median survival 15 mo）. Twenty-seven percent of these patients only received best supportive care （median survival 6 mo）, while 16% underwent surgery for their recurrence. Survival was best in the latter group （median survival 32 mo）.
CONCLUSION： Although treatment options and survival are limited in case of recurrent rectal cancer after radical local resection obtained with TME, patients can benefit from additional treatment, especially if a radical resection is feasible.
Matching donor red blood cells based on recipient antigens prevents alloimmunisation. Knowledge about the immunogenicity of red-blood-cell antigens can help optimise risk-adapted matching strategies. ...We set out to assess the immunogenicity of red-blood-cell antigens.
In an incident new-user cohort of previously non-transfused, non-alloimmunised white patients receiving non-extended matched red-blood-cell transfusions in six Dutch hospitals between 2006 and 2013, we determined the cumulative number of mismatched red-blood-cell units per patient. We used multiple imputation to address missing antigen data. Using Kaplan-Meier analysis, we estimated cumulative alloimmunisation incidences per mismatched antigen dose as a measure of immunogenicity.
Of 54 347 patients assessed, 21 512 were included in our study. Alloantibodies occurred in 474 (2·2%) of all transfused patients, with cumulative alloimmunisation incidences increasing up to 7·7% (95% CI 4·9-11·2) after 40 units received. The antigens C, c, E, K, and Jk(a) were responsible for 78% of all alloimmunisations in our cohort. K, E, and C(w) were the most immunogenic antigens (cumulative immunisation incidences after 2 mismatched units of 2·3% 95% CI 1·0-4·8 for K, 1·5% 0·6-3·0 for E, and 1·2% 0·0-10·8 for C(w)). These antigens were 8·7 times (for K), 5·4 times (for E), and 4·6 times (for C(w)) as immunogenic as Fy(a). The next most immunogenic antigens were, in order, e (1·9 times as immunogenic as Fy(a)), Jk(a) (1·9 times), and c (1·6 times).
Red-blood-cell antigens vary in their potency to evoke a humoral immune response. Our findings highlight that donor-recipient red-blood-cell matching strategies will be most efficient when primarily focusing on prevention of C, c, E, K, and Jk(a) alloimmunisation. Matching for Fy(a) is of lower clinical relevance. Variations of antigen frequencies determined by ethnic background prevent extrapolating these conclusions to non-white populations.
None.
No validated prognostic tool is available for predicting overall survival (OS) of patients with well-differentiated neuroendocrine tumors (WDNETs). This study, conducted in three independent cohorts ...of patients from five different European countries, aimed to develop and validate a classification prognostic score for OS in patients with stage IV WDNETs. We retrospectively collected data on 1387 patients: (i) patients treated at the Istituto Nazionale Tumori (Milan, Italy;
= 515); (ii) European cohort of rare NET patients included in the European RARECAREnet database (
= 457); (iii) Italian multicentric cohort of pancreatic NET (pNETs) patients treated at 24 Italian institutions (
= 415). The score was developed using data from patients included in cohort (i) (training set); external validation was performed by applying the score to the data of the two independent cohorts (ii) and (iii) evaluating both calibration and discriminative ability (Harrell C statistic). We used data on age, primary tumor site, metastasis (synchronous vs metachronous), Ki-67, functional status and primary surgery to build the score, which was developed for classifying patients into three groups with differential 10-year OS: (I) favorable risk group: 10-year OS ≥70%; (II) intermediate risk group: 30% ≤ 10-year OS < 70%; (III) poor risk group: 10-year OS <30%. The Harrell C statistic was 0.661 in the training set, and 0.626 and 0.601 in the RARECAREnet and Italian multicentric validation sets, respectively. In conclusion, based on the analysis of three 'field-practice' cohorts collected in different settings, we defined and validated a prognostic score to classify patients into three groups with different long-term prognoses.
In this nationwide, population-based study, we assessed 10-year relative survival among 225,305 patients with ten early-stage cancers diagnosed in the Netherlands during 2004-2015. This study aimed ...to ascertain which early-stage cancer is associated with minimal or no excess mortality and likely to be diagnosed in individuals who are otherwise more healthy or health-conscious than their counterparts in the general population. Ten-year relative survival marginally exceeded 100% in patients with early-stage prostate cancer, while it was close to 100% for patients with ductal carcinoma in situ (DCIS) and stage I cancers of the breast, skin (melanoma), testis, and thyroid. In contrast, patients with early-stage oral/pharyngeal, bladder, lung, and pancreatic cancers experienced considerable excess mortality, reflected by a 10-year relative survival of 74.9%, 69.4%, 45.5%, and 33.9%, respectively. Collectively, the life expectancy of patients with DCIS and early-stage cancers of the prostate, breast, skin (melanoma), testis, and thyroid parallels the expected survival of an age-, sex-, and calendar year-matched group from the general population. Our study findings add to the controversy surrounding overdiagnosis of particular early-stage cancers that are generally not destined to metastasis or cause excess mortality.
Red cell alloimmunization may induce severe hemolytic side effects. Identification of risk-modifying conditions will help tailor preventative strategies. This study aims to quantify the associations ...of hematologic malignancies and solid cancers with red cell alloimmunization in patients receiving red cell transfusions. We performed a nested multicenter case-control study in a source population of 24,063 patients receiving their first and subsequent red cell transfusions during an 8-year follow-up period. Cases (n=505), defined as patients developing a first transfusion-induced red cell alloantibody, were each compared with 2 non-alloimmunized controls (n=1010) who received a similar number of red cell units. Using multivariate logistic regression analyses, we evaluated the association of various malignancies and treatment regimens with alloimmunization during a delineated 5-week risk period. The incidence of alloimmunization among patients with acute (myeloid or lymphoid) leukemia and mature (B- or T-cell) lymphoma was significantly reduced compared to patients without these malignancies: adjusted relative risks (RR) with 95% confidence interval (CI) 0.36 (range 0.19-0.68) and 0.30 (range 0.12-0.81). Associations were primarily explained by immunosuppressive treatments RR for (any type of) chemotherapy combined with immunotherapy 0.27 (95%CI: 0.09-0.83). Alloimmunization risks were similarly diminished in allogeneic or autologous stem cell transplanted patients (RR 0.34, 95%CI: 0.16-0.74), at least during the six months post transplant. Alloimmunization risks of patients with other hematologic diseases or solid cancers, and their associated treatment regimens were similar to risks in the general transfused population. Our findings suggest that, in contrast to malignancies in general, hemato-oncological patients treated with dose-intensive regimens have strongly diminished risk of red cell alloimmunization.
Population-based studies assessing long-term patterns of incidence and disease characteristics of germ cell tumors (GCTs) in children are scarce. We investigated incidence and survival trends of ...malignant extracranial GCTs in children using population-based nationwide data from the Netherlands.
All malignant extracranial GCTs diagnosed in patients aged 0–18 years between 1990 and 2018 were selected from the Netherlands Cancer Registry. Incidence rates were calculated as the average annual number of cases per 1 million person-years. Five-year overall survival (OS) was calculated.
A total of 815 cases were identified. Gonadal GCTs (n=665, testis n=485, ovarian n=180) were more common than extragonadal GCTs (n=149). Stage distribution for testicular and extragonadal GCTs shifted between 1990 and 2004 and 2005–2018 towards more localized disease. The overall incidence remained stable over time, but a significant increase was noted for extragonadal GCTs in the 0–9 years age group. Survival of extragonadal GCTs (5-year OS 84.1%, 95% CI 77.1–89.1), in particular mediastinal GCTs (5-year OS 66.7%, 95% CI 45.7–81.1), was lower than that of gonadal GCTs (5-year OS testis 95.0%, 95% CI 92.7–96.7;ovary 97.8%, 95% CI 94.2–99.2). The 5-year OS of our entire cohort was 93.6% (95% CI 91.7–95.1). Five-year OS significantly increased from 89.5% (95% CI 86.1–92.2) in 1990–2004–97.4% (95% CI 95.3–98.5) in 2005–2018.
Although the incidence of all malignant pediatric extracranial GCTs remained stable during 1990–2018, an increase was observed for extragonadal GCTs in younger children (0–9 years). There was a shift towards more localized disease for testicular and extragonadal GCTs. Five-year OS increased over time exceeding 90% (91.4%, 95% CI 82.7–95.8) in the most recent diagnostic period. Mediastinal GCTs had the lowest OS, supporting the need for future research.
•The first comprehensive population-based study on pediatric GCTs in the Netherlands.•815 children were diagnosed with a malignant extracranial GCT in the Netherlands.•We saw a significant increase in incidence for extragonadal GCTs in 0–9 yr old children.•5 yr overall survival of all malignant GCTs increased significantly over time towards 98%.•Survival was poorest for extragonadal, and in particular for mediastinal GCTs.
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