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Sweden: cancer statistics from IARC GlobalCan (2012)

Population in 2012: 9.5m
People newly diagnosed with cancer (excluding NMSC) / yr: 50,500
Age-standardised rate, incidence per 100,000 people/yr: 270.0
Risk of getting cancer before age 75:27.8%
People dying from cancer /yr: 22,100

Menu: Swedish Cancer Resources

Swedish Cancer Organisations
Cancer Centres in Sweden
Latest Research Publications from Sweden

Swedish Cancer Organisations (16 links)

Cancer Centres in Sweden (6 links)

Latest Research Publications from Sweden

Hillmen P, Robak T, Janssens A, et al.
Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open-label phase 3 trial.
Lancet. 2015; 385(9980):1873-83 [PubMed] Related Publications
BACKGROUND: Treatment for patients with chronic lymphocytic leukaemia who are elderly or who have comorbidities is challenging because fludarabine-based chemoimmunotherapies are mostly not suitable. Chlorambucil remains the standard of care in many countries. We aimed to investigate whether the addition of ofatumumab to chlorambucil could lead to better clinical outcomes than does treatment with chlorambucil alone, while also being tolerable for patients who have few treatment options.
METHODS: We carried out a randomised, open-label, phase 3 trial for treatment-naive patients with chronic lymphocytic leukaemia in 109 centres in 16 countries. We included patients who had active disease needing treatment, but in whom fludarabine-based treatment was not possible. We randomly assigned patients (1:1) to receive oral chlorambucil (10 mg/m(2)) on days 1-7 of a 28 day treatment course or to receive chlorambucil by this schedule plus intravenous ofatumumab (cycle 1: 300 mg on day 1 and 1000 mg on day 8; subsequent cycles: 1000 mg on day 1) for three to 12 cycles. Assignment was done with a randomisation list that was computer generated at GlaxoSmithKline, and was stratified, in a block size of two, by age, disease stage, and performance status. The primary endpoint was progression-free survival in the intention-to-treat population and assessment was done by an independent review committee that was masked to group assignment. The study is registered with ClinicalTrials.gov, number NCT00748189.
FINDINGS: We enrolled 447 patients, median age 69 years (range 35-92). Between Dec 22, 2008, and May 26, 2011, we randomly assigned 221 patients to chlorambucil plus ofatumumab and 226 patients to chlorambucil alone. Median progression-free survival was 22·4 months (95% CI 19·0-25·2) in the group assigned to chlorambucil plus ofatumumab compared with 13·1 months (10·6-13·8) in the group assigned to chlorambucil only (hazard ratio 0·57, 95% CI 0·45-0·72; p<0·0001). Grade 3 or greater adverse events were more common in the chlorambucil plus ofatumumab group (109 [50%] patients; vs 98 [43%] given chlorambucil alone), with neutropenia being the most common event (56 [26%] vs 32 [14%]). Grade 3 or greater infections had similar frequency in both groups. Grade 3 or greater infusion-related adverse events were reported in 22 (10%) patients given chlorambucil plus ofatumumab. Five (2%) patients died during treatment in each group.
INTERPRETATION: Addition of ofatumumab to chlorambucil led to clinically important improvements with a manageable side-effect profile in treatment-naive patients with chronic lymphocytic leukaemia who were elderly or had comorbidities. Chlorambucil plus ofatumumab is therefore an important treatment option for these patients who cannot tolerate more intensive therapy.
FUNDING: GlaxoSmithKline, Genmab A/S.

Related: Monoclonal Antibodies Chlorambucil Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology

Mavaddat N, Pharoah PD, Michailidou K, et al.
Prediction of breast cancer risk based on profiling with common genetic variants.
J Natl Cancer Inst. 2015; 107(5) [PubMed] Related Publications
BACKGROUND: Data for multiple common susceptibility alleles for breast cancer may be combined to identify women at different levels of breast cancer risk. Such stratification could guide preventive and screening strategies. However, empirical evidence for genetic risk stratification is lacking.
METHODS: We investigated the value of using 77 breast cancer-associated single nucleotide polymorphisms (SNPs) for risk stratification, in a study of 33 673 breast cancer cases and 33 381 control women of European origin. We tested all possible pair-wise multiplicative interactions and constructed a 77-SNP polygenic risk score (PRS) for breast cancer overall and by estrogen receptor (ER) status. Absolute risks of breast cancer by PRS were derived from relative risk estimates and UK incidence and mortality rates.
RESULTS: There was no strong evidence for departure from a multiplicative model for any SNP pair. Women in the highest 1% of the PRS had a three-fold increased risk of developing breast cancer compared with women in the middle quintile (odds ratio [OR] = 3.36, 95% confidence interval [CI] = 2.95 to 3.83). The ORs for ER-positive and ER-negative disease were 3.73 (95% CI = 3.24 to 4.30) and 2.80 (95% CI = 2.26 to 3.46), respectively. Lifetime risk of breast cancer for women in the lowest and highest quintiles of the PRS were 5.2% and 16.6% for a woman without family history, and 8.6% and 24.4% for a woman with a first-degree family history of breast cancer.
CONCLUSIONS: The PRS stratifies breast cancer risk in women both with and without a family history of breast cancer. The observed level of risk discrimination could inform targeted screening and prevention strategies. Further discrimination may be achievable through combining the PRS with lifestyle/environmental factors, although these were not considered in this report.

Related: Breast Cancer

Rodrigues G, Oberije C, Senan S, et al.
Is intermediate radiation dose escalation with concurrent chemotherapy for stage III non-small-cell lung cancer beneficial? A multi-institutional propensity score matched analysis.
Int J Radiat Oncol Biol Phys. 2015; 91(1):133-9 [PubMed] Related Publications
PURPOSE: The clinical benefits and risks of dose escalation (DE) for stage III non-small-cell lung cancer (NSCLC) remain uncertain despite the results from Radiation Therapy Oncology Group (RTOG) protocol 0617. There is significant heterogeneity of practice, with many clinicians prescribing intermediate dose levels between the 0617 study arms of 60 and 74 Gy. This study investigated whether this strategy is associated with any survival benefits/risks by analyzing a large multi-institutional database.
METHODS AND MATERIALS: An individual patient database of stage III NSCLC patients treated with radical intent concurrent chemoradiation therapy was created (13 institutions, n=1274 patients). Patients were divided into 2 groups based on tumor Biological Effective Dose at 10 Gy (BED 10): those receiving standard dose (SD; n=552), consisting of 72Gy ≤ BED 10 ≤ 76.8 Gy (eg 60-64 Gy/30-32 fractions [fr]), and those receiving intermediate dose (ID; n=497), consisting of 76.8Gy < BED 10 < 100.8 Gy (eg >64 Gy/32 fr and <74 Gy/37 fr), with lower-dose patients (n=225) excluded from consideration. Patients were then matched using propensity scores, leading to 2 matched groups of 196 patients. Outcomes were compared using various statistics including interquartile range (IQR), Kaplan-Meier curves, and adjusted Cox regression analysis.
RESULTS: Matched groups were found to be balanced except for N stage (more N3 disease in SD), median treatment year (SD in 2003; ID in 2007), platinum and taxane chemotherapy (SD in 28%; ID in 39%), and median follow-up (SD were 89 months; ID were 40 months). Median dose fractionation was 60 Gy/30 fr in SD (BED 10 IQR: 72.0-75.5 Gy) and 66 Gy/33 fr (BED 10 IQR: 78.6-79.2 Gy) in ID. Survival curves for SD and ID matched cohorts were statistically similar (P=.27); however, a nonstatistically significant trend toward better survival for ID was observed after 15 months (median survival SD: 19.3 months; ID: 21.0 months). There was an increase in grades III to V lung toxicity associated with ID (13.0% vs 4.9%, respectively).
CONCLUSIONS: No significant overall survival benefits were found with intermediate DE; however, more grade III or greater lung toxicity was observed. The separation of survival curves after 15 months of follow-up suggests that a small overall survival improvement associated with intermediate DE cannot be excluded.

Related: Non-Small Cell Lung Cancer Cisplatin Lung Cancer

Fager M, Toma-Dasu I, Kirk M, et al.
Linear energy transfer painting with proton therapy: a means of reducing radiation doses with equivalent clinical effectiveness.
Int J Radiat Oncol Biol Phys. 2015; 91(5):1057-64 [PubMed] Related Publications
PURPOSE: The purpose of this study was to propose a proton treatment planning method that trades physical dose (D) for dose-averaged linear energy transfer (LETd) while keeping the radiobiologically weighted dose (DRBE) to the target the same.
METHODS AND MATERIALS: The target is painted with LETd by using 2, 4, and 7 fields aimed at the proximal segment of the target (split target planning [STP]). As the LETd within the target increases with increasing number of fields, D decreases to maintain the DRBE the same as the conventional treatment planning method by using beams treating the full target (full target planning [FTP]).
RESULTS: The LETd increased 61% for 2-field STP (2STP) compared to FTP, 72% for 4STP, and 82% for 7STP inside the target. This increase in LETd led to a decrease of D with 5.3 ± 0.6 Gy for 2STP, 4.4 ± 0.7 Gy for 4STP, and 5.3 ± 1.1 Gy for 7STP, keeping the Drbe at 90% of the volume (Drbe, 90) constant to FTP.
CONCLUSIONS: LETd painting offers a method to reduce prescribed dose at no cost to the biological effectiveness of the treatment.

Related: Prostate Cancer

Bonjer HJ, Deijen CL, Abis GA, et al.
A randomized trial of laparoscopic versus open surgery for rectal cancer.
N Engl J Med. 2015; 372(14):1324-32 [PubMed] Related Publications
BACKGROUND: Laparoscopic resection of colorectal cancer is widely used. However, robust evidence to conclude that laparoscopic surgery and open surgery have similar outcomes in rectal cancer is lacking. A trial was designed to compare 3-year rates of cancer recurrence in the pelvic or perineal area (locoregional recurrence) and survival after laparoscopic and open resection of rectal cancer.
METHODS: In this international trial conducted in 30 hospitals, we randomly assigned patients with a solitary adenocarcinoma of the rectum within 15 cm of the anal verge, not invading adjacent tissues, and without distant metastases to undergo either laparoscopic or open surgery in a 2:1 ratio. The primary end point was locoregional recurrence 3 years after the index surgery. Secondary end points included disease-free and overall survival.
RESULTS: A total of 1044 patients were included (699 in the laparoscopic-surgery group and 345 in the open-surgery group). At 3 years, the locoregional recurrence rate was 5.0% in the two groups (difference, 0 percentage points; 90% confidence interval [CI], -2.6 to 2.6). Disease-free survival rates were 74.8% in the laparoscopic-surgery group and 70.8% in the open-surgery group (difference, 4.0 percentage points; 95% CI, -1.9 to 9.9). Overall survival rates were 86.7% in the laparoscopic-surgery group and 83.6% in the open-surgery group (difference, 3.1 percentage points; 95% CI, -1.6 to 7.8).
CONCLUSIONS: Laparoscopic surgery in patients with rectal cancer was associated with rates of locoregional recurrence and disease-free and overall survival similar to those for open surgery. (Funded by Ethicon Endo-Surgery Europe and others; COLOR II ClinicalTrials.gov number, NCT00297791.).

Höglund M, Sandin F, Simonsson B
Epidemiology of chronic myeloid leukaemia: an update.
Ann Hematol. 2015; 94 Suppl 2:S241-7 [PubMed] Related Publications
National and regional population-based registries are, provided diagnostic accuracy and full coverage of the target population, indispensible tools for epidemiological research. Chronic myeloid leukaemia (CML) registries with more comprehensive reporting may also provide complementary data on treatment outcome to those obtained from clinical trials. Reports from several European CML registries consistently show a crude annual incidence of 0.7-1.0/100,000, a median age at diagnosis of 57-60 years and a male/female ratio of 1.2-1.7. The incidence of CML has been stable over time. Worldwide, variations in the reported incidence of CML may be due to methodological issues, but a true difference between different geographical areas and/or ethnical subgroups cannot be excluded. The prevalence of CML is not well known but has been estimated to be 10-12/100,000 inhabitants with a steady increase due to the dramatic improvement in survival of these patients. In recent population-based studies, CML patients have an overall survival that is comparable to that shown in large clinical trials, though relative survival in patients >70 years is still decreased. The importance of socio-economic factors and health-care setting for outcome and the possible increased risk of secondary cancer in CML are areas of ongoing research.

Related: Chronic Myeloid Leukemia (CML) CML - Molecular Biology

Lin CY, Gustafsson JÅ
Targeting liver X receptors in cancer therapeutics.
Nat Rev Cancer. 2015; 15(4):216-24 [PubMed] Related Publications
Members of the nuclear receptor superfamily of ligand-dependent transcription factors carry out vital cellular functions and are highly druggable therapeutic targets. Liver X receptors (LXRs) are nuclear receptor family members that function in cholesterol transport, glucose metabolism and the modulation of inflammatory responses. There is now accumulating evidence to support the involvement of LXRs in a variety of malignancies and the potential efficacy of their ligands in these diseases. This Review summarizes the discovery and characterization of LXRs and their ligands, their effects and mechanisms in preclinical cancer models, and the future directions of basic and translational LXR research in cancer therapeutics.

Related: Cancer Prevention and Risk Reduction

Michailidou K, Beesley J, Lindstrom S, et al.
Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer.
Nat Genet. 2015; 47(4):373-80 [PubMed] Related Publications
Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

Related: Breast Cancer

Rubio CA, Kaufeldt A, Kohan R, et al.
β-catenin Helices in the cytoplasm of sporadic and FAP duodenal adenomas.
Anticancer Res. 2015; 35(3):1433-6 [PubMed] Related Publications
BACKGROUND: Initiation and progression in conventional adenomas is triggered by deregulation of Wnt/β-catenin signaling. In the absence of Wnt signal (off-state), β-catenin prevents phosphorylation of glycogen synthase kinase (GSK)-3β leading to aberrant nuclear accumulation in human tumors. While investigating the nuclear expression of β-catenin in biopsies from duodenal adenomas, we observed a non-previously reported phenomenon, namely the presence of β-catenin cytoplasmic helices (coils).
MATERIALS AND METHODS: Sections from 39 biopsies were immunostained with β-catenin: 25 from duodenal adenomas and the remaining 14 had normal duodenal mucosa (n=11) or polypoid gastric duodenal metaplasia (n=3).
RESULTS: Eighteen out of the 25 duodenal adenomas (72%) showed β-catenin helices; in contrast, none of the 33 control biopsies (including those with normal duodenal mucosa, gastric duodenal metaplasia and normal mucosa adjacent to 19 adenomas) showed β-catenin helices (p<0.05). The review of diagnostic H&E-stained sections and of β-catenin-stained nuclei revealed that the dysplastic nuclei were arranged in a picket fence-like fashion along the basement membrane of the glands and not as loops within the dysplastic glands; the nuclei of the dysplastic glands were not forming part of the β-catenin helices.
DISCUSSION: If these β-catenin coils are unrelated to an abnormal nuclear distribution at the base of the dysplastic glands, the rational explanation might be that the helices highlight changes taking place in the cytoplasm of affected glandular cells.
CONCLUSION: According to some authors, mutations in the β-catenin genes are always associated with a morphologically neoplastic course. It is herein proposed that β-catenin helices in duodenal adenomas might uncover a novel cytoplasmic phenomenon ensuing during the adenoma-carcinoma pathway.

Related: Familial Adenomatous Polyposis (FAP) CTNNB1 gene

Tanskanen T, Gylfe AE, Katainen R, et al.
Systematic search for rare variants in Finnish early-onset colorectal cancer patients.
Cancer Genet. 2015 Jan-Feb; 208(1-2):35-40 [PubMed] Related Publications
The heritability of colorectal cancer (CRC) is incompletely understood, and the contribution of undiscovered rare variants may be important. In search of rare disease-causing variants, we exome sequenced 22 CRC patients who were diagnosed before the age of 40 years. Exome sequencing data from 95 familial CRC patients were available as a validation set. Cases with known CRC syndromes were excluded. All patients were from Finland, a country known for its genetically homogenous population. We searched for rare nonsynonymous variants with allele frequencies below 0.1% in 3,374 Finnish and 58,112 non-Finnish controls. In addition, homozygous and compound heterozygous variants were studied. No genes with rare loss-of-function variants were present in more than one early-onset CRC patient. Three genes (ADAMTS4, CYTL1, and SYNE1) harbored rare loss-of-function variants in both early-onset and familial CRC cases. Five genes with homozygous variants in early-onset CRC cases were found (MCTP2, ARHGAP12, ATM, DONSON, and ROS1), including one gene (MCTP2) with a homozygous splice site variant. All discovered homozygous variants were exclusive to one early-onset CRC case. Independent replication is required to associate the discovered variants with CRC. These findings, together with a lack of family history in 19 of 22 (86%) early-onset patients, suggest genetic heterogeneity in unexplained early-onset CRC patients, thus emphasizing the requirement for large sample sizes and careful study designs to elucidate the role of rare variants in CRC susceptibility.

Related: Colorectal (Bowel) Cancer

van der Schaaf M, Johar A, Wijnhoven B, et al.
Extent of lymph node removal during esophageal cancer surgery and survival.
J Natl Cancer Inst. 2015; 107(5) [PubMed] Related Publications
BACKGROUND: It is unclear how the extent of surgical lymph node clearance influences prognosis after surgery for esophageal cancer.
METHODS: This nationwide, population-based cohort study included 1044 esophageal cancer patients who had undergone esophagectomy between 1987 and 2010 in Sweden, with follow-up until 2012. The independent role of lymph node removal in relation to survival was analyzed using Cox proportional hazards regression, providing hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for age, sex, comorbidity, tumor (T) stage, neo-adjuvant treatment, surgeon volume, and calendar period. Statistical tests were two-sided, except tests for trend.
RESULTS: Analyzed as a linear variable, a higher number of lymph nodes removed did not influence the overall five-year mortality (adjusted HR = 1.00, 95% CI = 0.99 to 1.01). Patients in the third (7-15 nodes) and fourth (16-114 nodes) quartiles of removed nodes did not demonstrate any decreased overall five-year mortality compared with those in the lowest two quartiles (<7 nodes) (HR = 1.13, 95% CI = 0.95 to 1.35 and HR = 1.17, 95% CI = 0.94 to 1.46, respectively). In early T stages (Tis-T1) the hazard ratios indicated a worse survival with more lymphadenectomy using the median as cutoff (HR = 1.53, 95% CI = 1.13 to 2.06). Increased lymph node removal did not decrease mortality in any specific T stage. A greater number of metastatic nodes and a higher positive-to-negative node ratio were associated with strongly increased mortality. All results were similar when disease-specific mortality was analyzed.
CONCLUSION: This population-based study indicates that more extensive lymph node clearance during surgery for esophageal cancer may not improve survival. These results challenge current clinical guidelines, and further research is needed to change clinical practice.

Related: Cancer of the Esophagus Esophageal Cancer

Rutherford MJ, Abel GA, Greenberg DC, et al.
The impact of eliminating age inequalities in stage at diagnosis on breast cancer survival for older women.
Br J Cancer. 2015; 112 Suppl 1:S124-8 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Older women with breast cancer have poorer relative survival outcomes, but whether achieving earlier stage at diagnosis would translate to substantial reductions in mortality is uncertain.
METHODS: We analysed data on East of England women with breast cancer (2006-2010) aged 70+ years. We estimated survival for different stage-deprivation-age group strata using both the observed and a hypothetical stage distribution (assuming that all women aged 75+ years acquired the stage distribution of those aged 70-74 years). We subsequently estimated deaths that could be postponed beyond 5 years from diagnosis if women aged 75+ years had the hypothetical stage distribution. We projected findings to the English population using appropriate age and socioeconomic group weights.
RESULTS: For a typically sized annual cohort in the East of England, 27 deaths in women with breast cancer aged 75+ years can be postponed within 5 years from diagnosis if their stage distribution matched that of the women aged 70-74 years (4.8% of all 566 deaths within 5 years post diagnosis in this population). Under assumptions, we estimate that the respective number for England would be 280 deaths (5.0% of all deaths within 5 years post diagnosis in this population).
CONCLUSIONS: The findings support ongoing development of targeted campaigns aimed at encouraging prompt presentation in older women.

Related: Breast Cancer

Rutherford MJ, Ironmonger L, Ormiston-Smith N, et al.
Estimating the potential survival gains by eliminating socioeconomic and sex inequalities in stage at diagnosis of melanoma.
Br J Cancer. 2015; 112 Suppl 1:S116-23 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Although inequalities in cancer survival are thought to reflect inequalities in stage at diagnosis, little evidence exists about the size of potential survival gains from eliminating inequalities in stage at diagnosis.
METHODS: We used data on patients diagnosed with malignant melanoma in the East of England (2006-2010) to estimate the number of deaths that could be postponed by completely eliminating socioeconomic and sex differences in stage at diagnosis after fitting a flexible parametric excess mortality model.
RESULTS: Stage was a strong predictor of survival. There were pronounced socioeconomic and sex inequalities in the proportion of patients diagnosed at stages III-IV (12 and 8% for least deprived men and women and 25 and 18% for most deprived men and women, respectively). For an annual cohort of 1025 incident cases in the East of England, eliminating sex and deprivation differences in stage at diagnosis would postpone approximately 24 deaths to beyond 5 years from diagnosis. Using appropriate weighting, the equivalent estimate for England would be around 215 deaths, representing 11% of all deaths observed within 5 years from diagnosis in this population.
CONCLUSIONS: Reducing socioeconomic and sex inequalities in stage at diagnosis would result in substantial reductions in deaths within 5 years of a melanoma diagnosis.

Related: Melanoma Skin Cancer

O'Farrell S, Garmo H, Holmberg L, et al.
Risk and timing of cardiovascular disease after androgen-deprivation therapy in men with prostate cancer.
J Clin Oncol. 2015; 33(11):1243-51 [PubMed] Related Publications
PURPOSE: Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent.
METHODS: By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models.
RESULTS: From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort.
CONCLUSION: Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

Related: Prostate Cancer

Andersson AK, Ma J, Wang J, et al.
The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias.
Nat Genet. 2015; 47(4):330-7 [PubMed] Related Publications
Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older children (MLL-R cases) with leukemia. Our data show that infant MLL-R ALL has one of the lowest frequencies of somatic mutations of any sequenced cancer, with the predominant leukemic clone carrying a mean of 1.3 non-silent mutations. Despite this paucity of mutations, we detected activating mutations in kinase-PI3K-RAS signaling pathway components in 47% of cases. Surprisingly, these mutations were often subclonal and were frequently lost at relapse. In contrast to infant cases, MLL-R leukemia in older children had more somatic mutations (mean of 6.5 mutations/case versus 1.3 mutations/case, P = 7.15 × 10(-5)) and had frequent mutations (45%) in epigenetic regulators, a category of genes that, with the exception of MLL, was rarely mutated in infant MLL-R ALL.

Related: Acute Lymphocytic Leukemia (ALL) Signal Transduction MLL gene

Aleksandrova K, Chuang SC, Boeing H, et al.
A prospective study of the immune system activation biomarker neopterin and colorectal cancer risk.
J Natl Cancer Inst. 2015; 107(4) [PubMed] Article available free on PMC after 01/04/2016 Related Publications
BACKGROUND: Neopterin may be relevant for colorectal cancer (CRC) development, as a biomarker of cellular immune activity exerting pleiotropic effects on cellular ageing, oxidative stress, and inflammation. So far, the association between prediagnostic neopterin and colon and rectal cancer risk has not been evaluated in human populations.
METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort using data on plasma concentrations of total neopterin (T-N, sum of neopterin and 7,8-dihydroneopterin) in 830 incident CRC case patients (561 colon and 269 rectal) matched within risk sets to 830 control participants. A subsequent replication study used data from the Hordaland Health Study, where 173 CRC case patients have been diagnosed among 6594 healthy participants over 12 years of follow-up.
RESULTS: After multivariable adjustment for a priori chosen CRC risk factors, a "U-shaped" association of T-N with CRC was revealed. Compared with the second quintile of the T-N distribution, the relative risks for the first, third, fourth, and fifth quintiles were 2.37 (95% CI = 1.66 to 3.39), 1.24 (95% CI = 0.87 to 1.77), 1.55 (95% CI = 1.08 to 2.22), and 2.31 (95% CI = 1.63 to 3.27), respectively. Replication of these associations within the Hordaland Health Study yielded similar results. No differences have been observed when the associations were explored by colon and rectal cancer site (two-sided P difference = .87) and after excluding case patients diagnosed within the first four follow-up years.
CONCLUSIONS: These novel findings provide evidence of the role of both suppressed and activated cell-mediated immunity as reflected by prediagnostic T-N concentrations in the development of CRC.

Related: Colorectal (Bowel) Cancer

Derogar M, Blomberg J, Sadr-Azodi O
Hospital teaching status and volume related to mortality after pancreatic cancer surgery in a national cohort.
Br J Surg. 2015; 102(5):548-57; discussion 557 [PubMed] Related Publications
BACKGROUND: The association between hospital teaching status and mortality after pancreatic resection is not well explored. Although hospital volume is related to short-term mortality, the effect on long-term survival needs investigation, taking into account hospital teaching status and selective referral patterns.
METHODS: This was a nationwide retrospective register-based cohort study of patients undergoing pancreatic resection between 1990 and 2010. Follow-up for survival was carried out until 31 December 2011. The associations between hospital teaching status and annual hospital volume and short-, intermediate- and long-term mortality were determined by use of multivariable Cox regression models, which provided hazard ratios (HRs) with 95 per cent c.i. The analyses were mutually adjusted for hospital teaching status and volume, as well as for patients' sex, age, education, co-morbidity, type of resection, tumour site and histology, time interval, referral and hospital clustering.
RESULTS: A total of 3298 patients were identified during the study interval. Hospital teaching status was associated with a decrease in overall mortality during the latest interval (years 2005-2010) (university versus non-university hospitals: HR 0·72, 95 per cent c.i. 0·56 to 0·91; P = 0·007). During all time periods, hospital teaching status was associated with decreased mortality more than 2 years after surgery (university versus non-university hospitals: HR 0·86, 0·75 to 0·98; P = 0·026). Lower annual hospital volume increased the risk of short-term mortality (HR for 3 or fewer compared with 4-6 pancreatic cancer resections annually: 1·60, 1·04 to 2·48; P = 0·034), but not long-term mortality. Sensitivity analyses with adjustment for tumour stage did not change the results.
CONCLUSION: Hospital teaching status was strongly related to decreased mortality in both the short and long term. This may relate to processes of care rather than volume per se. Very low-volume hospitals had the highest short-term mortality risk.

Related: Cancer of the Pancreas Pancreatic Cancer

Yang HP, Cook LS, Weiderpass E, et al.
Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).
Br J Cancer. 2015; 112(5):925-33 [PubMed] Article available free on PMC after 03/03/2016 Related Publications
BACKGROUND: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes.
METHODS: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).
RESULTS: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer.
CONCLUSIONS: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.

Related: Endometrial (Uterus) Cancer Endometrial Cancer

Yu M, Liu H, Duan Y, et al.
Four types of fatty acids exert differential impact on pancreatic cancer growth.
Cancer Lett. 2015; 360(2):187-94 [PubMed] Related Publications
Increased fatty acids (FAs) regulate pancreatic cancer progression, however, the detailed mechanism is not clear, and different forms of FAs may play diversified roles in pancreatic cancer. To elucidate the underlying mechanism, we compared the effects of four major types of FAs on pancreatic cancer growth both in cell culture and in a mouse model. HPAF pancreatic cancer cells were implanted in nude mice for 14 weeks, and the mice were fed with four different high-fat/high-energy diets (15% fat, 4 kcal/g), an iso-caloric diet (5% fat, 4 kcal/g) and a normal diet (4% fat, 3 kcal/g). The high fat diets were rich in saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and n-6 and n-3 polyunsaturated fatty acids (n6- and n3PUFAs), respectively. While n3PUFA diet decreased tumor viability, the other high fat diets stimulated tumor viability by apparently different mechanisms. For instance, xenografts whose carriers were fed with SFA diet had marked expression of cancer-related proteins and lipid droplets. Although mice that were fed with MUFA- and n6PUFA diets had pancreatic tumors of similar size, liver metastasis occurred more frequently in those with the n6PUFA diet. In experiments in vitro, the HPAF-cell population was increased by SFAs and MUFAs, decreased by n3PUFAs and not changed by n6PUFAs. In conclusion, different fatty acids have different impact on pancreatic cancer cells. The effects of fatty acids on pancreatic cancer cells were consistent in vivo and in vitro except that n6PUFAs only had regulatory effects in vivo.

Related: Cancer of the Pancreas Pancreatic Cancer

Hållmarker U, James S, Michaëlsson K, et al.
Cancer incidence in participants in a long-distance ski race (Vasaloppet, Sweden) compared to the background population.
Eur J Cancer. 2015; 51(4):558-68 [PubMed] Related Publications
BACKGROUND: We studied the association between taking part in a long distance ski race and cancer incidence to address the hypothesis that a lifestyle involving a high degree of physical activity (PA) lowers cancer incidence with a pattern that is different by cancer site.
METHODS: Cancer incidence was estimated in a large cohort of skiers (n=185,412) participating in the Vasaloppet long distance ski race in Sweden 1989-2010 and non-participants in the ski race, randomly selected from the Swedish general population (n=184,617). Data include race finishing times as a measurement of physical fitness. Hazard ratios (HRs) and net probability of cancer over twenty years of follow-up were estimated for all invasive cancer, and separately for prostate, breast, colo-rectal and lung cancer, and groups of cancers with presumed relation to lifestyle.
FINDINGS: Participating in Vasaloppet was associated with a relative risk reduction for all invasive cancer of 6% (95% confidence interval 2-9%) and a relative risk reduction of 32% (95% confidence interval 28-37%) of cancer sites where there is epidemiological evidence that smoking, bodyweight, regular PA and consumption of fruit and vegetables are aetiological factors. For skin cancer the risk was increased, as for prostate cancer. Skiers with shorter finishing times had lower incidence of cancer.
INTERPRETATION: This study indicates that it is unrealistic to reduce overall population cancer incidence drastically with life style. However, cancers that are epidemiologically associated with life style factors were significantly reduced by what presumably is a blend of non-smoking, normal body weight, sound dietary habits and PA. Our data thus provide additional support for present days' recommendations about life style prevention. Higher health awareness is associated with attendance to screening, which may explain our results for prostate cancer.
FUNDING: University fund, independent funds from an insurance company and a private foundation.

Related: Cancer Prevention and Risk Reduction

ten Dijke P, van Dam H
14-3-3ζ turns TGF-β to the dark side.
Cancer Cell. 2015; 27(2):151-3 [PubMed] Related Publications
TGF-β/SMAD signaling has long been known to exhibit a dual role in cancer, questioning what determines its context-dependent functions. In this issue of Cancer Cell, Xu and colleagues describe a critical role of the adaptor protein 14-3-3ζ in modulating SMAD activities by changing its interaction partners during breast cancer progression.

Related: Bone Cancers Breast Cancer TP53

Palmqvist T, Dos S Matias L, Marthinsen AB, et al.
Radiobiological treatment planning evaluation of inverse planning simulated annealing for cervical cancer high-dose-rate brachytherapy.
Anticancer Res. 2015; 35(2):935-9 [PubMed] Related Publications
AIM: To compare five inverse treatment plans with one conventional manually-optimized plan for cervical cancer brachytherapy (BT) using radiobiological parameters combined with dosimetric and volumetric parameters.
MATERIALS AND METHODS: Five inverse treatment plans were calculated using an inverse planning simulated annealing (IPSA) algorithm for each of four fractions for 12 cervical cancer patients treated with high-dose-rate (HDR) brachytherapy. The inverse treatment plans were compared to a manually-optimized plan used for the actual treatment of the patients. The comparison of the plans was performed with respect to the probability of cure without complication (P+).
RESULTS: Overall, the manually optimized plan scored the best results; however, the probability of cure without complication is within an acceptable clinical range for all the plans.
CONCLUSION: Although there are still considerable uncertainties in the radiobiological parameters, the radiobiological plan evaluation method presents itself as a potential complement to physical dosimetric methods.

Related: Brachytherapy Cervical Cancer

Rubio CA, Kaufeldt A, Koha R, et al.
β-catenin helices in the cytoplasm of sessile serrated adenoma/polyps and conventional colorectal adenomas.
Anticancer Res. 2015; 35(2):929-34 [PubMed] Related Publications
Initiation and progression in conventional adenomas is triggered by deregulation of WNT/β-catenin signaling. In the absence of WNT signal (off-state), β-catenin prevents phosphorylation of GSK3β, leading to aberrant nuclear accumulation in human tumors. It has been postulated that mutations in the β-catenin gene are always associated with a morphologically-neoplastic course. While investigating the nuclear expression of β-catenin in 170 colorectal biopsies, we observed a non-previously reported phenomenon, namely the presence of β-catenin cytoplasmic helices in 29% (n=7) of 24 sessile serrated adenoma/polyps (SSA/P), in 24% (n=13) of 54 adenomas, in 8% (n=3) of 38 specimens with IBD, but in none (0/54) with normal mucosa. The earliest β-catenin helices were found at the bottom of SSA/P glands (the domain of stem cells in the colorectal mucosa). It is submitted that β-catenin helices might highlight a non-previously described cytoplasmic phenomenon evolving during the serrated-carcinoma pathway in SSA/P, and during the adenoma-carcinoma pathway in conventional adenomas.

Related: Colorectal (Bowel) Cancer CTNNB1 gene

Asciutto KC, Henic E, Forslund O, et al.
Age influences the clinical significance of atypical glandular cells on cytology.
Anticancer Res. 2015; 35(2):913-9 [PubMed] Related Publications
AIM: To evaluate women with atypical glandular cells (AGC) or adenocarcinoma in situ (AIS) on cytology.
PATIENTS AND METHODS: Population-based data of cervical smears taken between 2008-2012 were analyzed.
RESULTS: Cancer was diagnosed in 107 out of 199 patients (54%) with AGC or AIS; 30 with cervical adenocarcinoma and 77 with endometrial cancer. All women with endometrial cancer were 50 years or older. In women younger than 50 years, cervical pre-cancerous lesions were found in 44 (47%) and cervical adenocarcinoma in 24 out of 92 cases (26%). High-risk HPV infection was found in 62 out of 103 women (60%). The detection rate of high-risk HPV at finding histopathological AGC, AIS, low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions or cervical cancer was 98% (95% confidence interval=0.903-1.000) (54/55).
CONCLUSION: AGC or AIS indicates endometrial neoplasia in women 50 years or older and pre-cancerous or invasive glandular cervical lesions in younger women. HPV testing seems to identify underlying cervical adenocarcinoma and high grade squamous intraepithelial lesions.

Related: Cervical Cancer

Nikberg M, Kindler C, Chabok A, et al.
Circumferential resection margin as a prognostic marker in the modern multidisciplinary management of rectal cancer.
Dis Colon Rectum. 2015; 58(3):275-82 [PubMed] Related Publications
BACKGROUND: A positive circumferential resection margin has been associated with a high risk of local recurrence and a decrease in survival in patients who have rectal cancer.
OBJECTIVE: The purpose of this study was to analyze the involvement of circumferential resection margin in local recurrence and survival in a multidisciplinary population-based setting by using tailored oncological therapy and surgery with total mesorectal excision.
DESIGN: Data were collected in a prospective database and retrospectively analyzed. Between 1996 and 2009, 448 patients with rectal cancer underwent a curative bowel resection.
SETTINGS: Population-based data were collected at a single institution in the county of Västmanland, Sweden.
RESULTS: Preoperative radiotherapy was delivered to 334 patients (74%); it was delivered to 35 patients (8%) concomitantly with preoperative chemotherapy. In 70 patients (16%), en bloc resections of the prostate and vagina were performed. Intraoperative perforations were seen in 7 patients (1.6%). The mesorectal fascia was assessed as complete in 117/118 cases. In 32 cases (7%), the circumferential resection margin was 1 mm or less. After a median follow-up of 68 months, 5 (1.1%) patients developed a local recurrence; one of them had circumferential resection margin involvement. The 5-year overall survival was 77%. In the multivariate analysis, the circumferential resection margin was not an independent factor for disease-free survival.
LIMITATIONS: Mesorectal fascia was not assessed before 2007. The findings might be explained by a type II error but, from a clinical perspective, enough patients were included to motivate the conclusion of the study.
CONCLUSIONS: Circumferential resection margin is an important measurement in rectal cancer pathology, but the correlation to local recurrence is much less than previously stated, probably because of oncological treatment and surgery that respects the mesorectal fascia and, when required, en bloc resections. Circumferential resection margin should not be used as a prognostic marker in the modern multidisciplinary management of rectal cancer.

Hojjat-Farsangi M
Novel and emerging targeted-based cancer therapy agents and methods.
Tumour Biol. 2015; 36(2):543-56 [PubMed] Related Publications
After several decades of uncovering the cancer features and following the improvement of therapeutic agents, however cancer remains as one of the major reasons of mortality. Chemotherapy is one of the main treatment options and has significantly improved the overall survival of cancer patients, but chemotherapeutic agents are highly toxic for normal cells. Therefore, there is a great unmet medical need to develop new therapeutic principles and agents. Targeted-based cancer therapy (TBCT) agents and methods have revolutionized the cancer treatment efficacy. Monoclonal antibodies (mAbs) and small molecule inhibitors (SMIs) are among the most effective agents of TBCT. These drugs have improved the prognosis and survival of cancer patients; however, the therapeutic resistance has subdued the effects. Several mechanisms lead to drug resistance such as mutations in the drug targets, activation of compensatory pathways, and intrinsic or acquired resistance of cancer stem cells. Therefore, new modalities, improving current generation of inhibitors and mAbs, and optimizing the combinational therapy regimens are necessary to decrease the current obstacles in front of TBCT. Moreover, the success of new TBCT agents such as mAbs, SMIs, and immunomodulatory agents has sparked further therapeutic modalities with novel targets to inhibit. Due to the lack of cumulative information describing different agents and methods of TBCT, this review focuses on the most important agents and methods of TBCT that are currently under investigation.

Related: Monoclonal Antibodies Cancer Prevention and Risk Reduction

Sackey H, Johansson H, Sandelin K, et al.
Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery.
Eur J Surg Oncol. 2015; 41(4):577-84 [PubMed] Related Publications
BACKGROUND: The primary aim was to compare long-term health-related quality of life (HRQoL) in patients undergoing sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND), with or without axillary metastases. Secondary aims were to a) investigate agreement between objectively measured and self-reported lymphoedema and b) compare, with respect to HRQoL, women with objective arm lymphoedema without subjective ratings and those with no objective but subjective ratings of arm lymphoedema.
METHODS: The three study groups were defined by axillary surgery: 1) SLNB alone (N = 140), 2) ALND in patients without axillary metastases (N = 125) and 3) ALND in patients with axillary metastases (N = 155). Preoperatively, one and three years postoperatively arm volume was measured and questionnaires regarding self-perceived symptoms of arm lymphoedema and HRQoL were completed (The Swedish Short Form-36 Health Survey, SF-36).
RESULTS: Out of the original 516 who had axillary surgery, 420 (81%) completed the study. There were no statistically significant differences in HRQoL between the three study groups. No statistically significant agreement was found between self-perceived and objectively measured arm lymphoedema. Women without self-perceived arm lymphoedema, regardless of objective arm lymphoedema or not, scored higher on all eight SF-36 domains than those who reported self-perceived arm lymphoedema.
CONCLUSION: Women reporting self-perceived arm lymphoedema, regardless of objective lymphoedema or not, have a decreased long-term health-related quality of life. This indicates that more attention should be given to the subjective reports of symptom in order to better help these women.

Related: Breast Cancer

Holm J, Humphreys K, Li J, et al.
Risk factors and tumor characteristics of interval cancers by mammographic density.
J Clin Oncol. 2015; 33(9):1030-7 [PubMed] Related Publications
PURPOSE: To compare tumor characteristics and risk factors of interval breast cancers and screen-detected breast cancers, taking mammographic density into account.
PATIENTS AND METHODS: Women diagnosed with invasive breast cancer from 2001 to 2008 in Stockholm, Sweden, with data on tumor characteristics (n = 4,091), risk factors, and mammographic density (n = 1,957) were included. Logistic regression was used to compare interval breast cancers with screen-detected breast cancers, overall and by highest and lowest quartiles of percent mammographic density.
RESULTS: Compared with screen-detected breast cancers, interval breast cancers in nondense breasts (≤ 20% mammographic density) were significantly more likely to exhibit lymph node involvement (odds ratio [OR], 3.55; 95% CI, 1.74 to 7.13) and to be estrogen receptor negative (OR, 4.05; 95% CI, 2.24 to 7.25), human epidermal growth factor receptor 2 positive (OR, 5.17; 95% CI, 1.64 to 17.01), progesterone receptor negative (OR, 2.63; 95% CI, 1.58 to 4.38), and triple negative (OR, 5.33; 95% CI, 1.21 to 22.46). In contrast, interval breast cancers in dense breasts (> 40.9% mammographic density) were less aggressive than interval breast cancers in nondense breasts (overall difference, P = .008) and were phenotypically more similar to screen-detected breast cancers. Risk factors differentially associated with interval breast cancer relative to screen-detected breast cancer after adjusting for age and mammographic density were family history of breast cancer (OR, 1.32; 95% CI, 1.02 to 1.70), current use of hormone replacement therapy (HRT; OR, 1.84; 95% CI, 1.38 to 2.44), and body mass index more than 25 kg/m(2) (OR, 0.49; 95% CI, 0.29 to 0.82).
CONCLUSION: Interval breast cancers in women with low mammographic density have the most aggressive phenotype. The effect of HRT on interval breast cancer risk is not fully explained by mammographic density. Family history is associated with interval breast cancers, possibly indicating disparate genetic background of screen-detected breast cancers and interval breast cancers.

Related: Breast Cancer Cancer Screening and Early Detection

Toma-Dasu I, Uhrdin J, Lazzeroni M, et al.
Evaluating tumor response of non-small cell lung cancer patients with ¹⁸F-fludeoxyglucose positron emission tomography: potential for treatment individualization.
Int J Radiat Oncol Biol Phys. 2015; 91(2):376-84 [PubMed] Related Publications
OBJECTIVE: To assess early tumor responsiveness and the corresponding effective radiosensitivity for individual patients with non-small cell lung cancer (NSCLC) based on 2 successive (18)F-fludeoxyglucose positron emission tomography (FDG-PET) scans.
METHODS AND MATERIALS: Twenty-six NSCLC patients treated in Maastricht were included in the study. Fifteen patients underwent sequential chemoradiation therapy, and 11 patients received concomitant chemoradiation therapy. All patients were imaged with FDG before the start and during the second week of radiation therapy. The sequential images were analyzed in relation to the dose delivered until the second image. An operational quantity, effective radiosensitivity, αeff, was determined at the voxel level. Correlations were sought between the average αeff or the fraction of negative αeff values and the overall survival at 2 years. Separate analyses were performed for the primary gross target volume (GTV), the lymph node GTV, and the clinical target volumes (CTVs).
RESULTS: Patients receiving sequential treatment could be divided into responders and nonresponders, using a threshold for the average αeff of 0.003 Gy(-1) in the primary GTV, with a sensitivity of 75% and a specificity of 100% (P<.0001). Choosing the fraction of negative αeff as a criterion, the threshold 0.3 also had a sensitivity of 75% and a specificity of 100% (P<.0001). Good prognostic potential was maintained for patients receiving concurrent chemotherapy. For lymph node GTV, the correlation had low statistical significance. A cross-validation analysis confirmed the potential of the method.
CONCLUSIONS: Evaluation of the early response in NSCLC patients showed that it is feasible to determine a threshold value for effective radiosensitivity corresponding to good response. It also showed that a threshold value for the fraction of negative αeff could also be correlated with poor response. The proposed method, therefore, has potential to identify candidates for more aggressive strategies to increase the rate of local control and also avoid exposing to unnecessary aggressive therapies the majority of patients responding to standard treatment.

Related: Non-Small Cell Lung Cancer Lung Cancer

Baliakas P, Agathangelidis A, Hadzidimitriou A, et al.
Not all IGHV3-21 chronic lymphocytic leukemias are equal: prognostic considerations.
Blood. 2015; 125(5):856-9 [PubMed] Article available free on PMC after 29/01/2016 Related Publications
An unresolved issue in chronic lymphocytic leukemia (CLL) is whether IGHV3-21 gene usage, in general, or the expression of stereotyped B-cell receptor immunoglobulin defining subset #2 (IGHV3-21/IGLV3-21), in particular, determines outcome for IGHV3-21-utilizing cases. We reappraised this issue in 8593 CLL patients of whom 437 (5%) used the IGHV3-21 gene with 254/437 (58%) classified as subset #2. Within subset #2, immunoglobulin heavy variable (IGHV)-mutated cases predominated, whereas non-subset #2/IGHV3-21 was enriched for IGHV-unmutated cases (P = .002). Subset #2 exhibited significantly shorter time-to-first-treatment (TTFT) compared with non-subset #2/IGHV3-21 (22 vs 60 months, P = .001). No such difference was observed between non-subset #2/IGHV3-21 vs the remaining CLL with similar IGHV mutational status. In conclusion, IGHV3-21 CLL should not be axiomatically considered a homogeneous entity with adverse prognosis, given that only subset #2 emerges as uniformly aggressive, contrasting non-subset #2/IGVH3-21 patients whose prognosis depends on IGHV mutational status as the remaining CLL.

Related: Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology

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