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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

Chinot OL, Wick W, Mason W, et al.
Bevacizumab plus radiotherapy-temozolomide for newly diagnosed glioblastoma.
N Engl J Med. 2014; 370(8):709-22 [PubMed] Related Publications
BACKGROUND: Standard therapy for newly diagnosed glioblastoma is radiotherapy plus temozolomide. In this phase 3 study, we evaluated the effect of the addition of bevacizumab to radiotherapy-temozolomide for the treatment of newly diagnosed glioblastoma.
METHODS: We randomly assigned patients with supratentorial glioblastoma to receive intravenous bevacizumab (10 mg per kilogram of body weight every 2 weeks) or placebo, plus radiotherapy (2 Gy 5 days a week; maximum, 60 Gy) and oral temozolomide (75 mg per square meter of body-surface area per day) for 6 weeks. After a 28-day treatment break, maintenance bevacizumab (10 mg per kilogram intravenously every 2 weeks) or placebo, plus temozolomide (150 to 200 mg per square meter per day for 5 days), was continued for six 4-week cycles, followed by bevacizumab monotherapy (15 mg per kilogram intravenously every 3 weeks) or placebo until the disease progressed or unacceptable toxic effects developed. The coprimary end points were investigator-assessed progression-free survival and overall survival.
RESULTS: A total of 458 patients were assigned to the bevacizumab group, and 463 patients to the placebo group. The median progression-free survival was longer in the bevacizumab group than in the placebo group (10.6 months vs. 6.2 months; stratified hazard ratio for progression or death, 0.64; 95% confidence interval [CI], 0.55 to 0.74; P<0.001). The benefit with respect to progression-free survival was observed across subgroups. Overall survival did not differ significantly between groups (stratified hazard ratio for death, 0.88; 95% CI, 0.76 to 1.02; P=0.10). The respective overall survival rates with bevacizumab and placebo were 72.4% and 66.3% at 1 year (P=0.049) and 33.9% and 30.1% at 2 years (P=0.24). Baseline health-related quality of life and performance status were maintained longer in the bevacizumab group, and the glucocorticoid requirement was lower. More patients in the bevacizumab group than in the placebo group had grade 3 or higher adverse events (66.8% vs. 51.3%) and grade 3 or higher adverse events often associated with bevacizumab (32.5% vs. 15.8%).
CONCLUSIONS: The addition of bevacizumab to radiotherapy-temozolomide did not improve survival in patients with glioblastoma. Improved progression-free survival and maintenance of baseline quality of life and performance status were observed with bevacizumab; however, the rate of adverse events was higher with bevacizumab than with placebo. (Funded by F. Hoffmann-La Roche; ClinicalTrials.gov number, NCT00943826.).

Related: Angiogenesis Inhibitors Dacarbazine Bevacizumab (Avastin) Temozolomide
From Aix-Marseille University, Assistance Publique-Hôpitaux de Marseille, Service de Neuro-Oncologie, Centre Hospitaliere Universitaire Timone, Marseille (O.L.C.), UFR de Santé, Médecine et Biologie Humaine, Bobigny (A.F.C.), and Assistance Publique-Hôpitaux de Paris (AP-HP), H&...


Belkić D, Belkić K
Molecular imaging in the framework of personalized cancer medicine.
Isr Med Assoc J. 2013; 15(11):665-72 [PubMed] Related Publications
With our increased understanding of cancer cell biology, molecular imaging offers a strategic bridge to oncology. This complements anatomic imaging, particularly magnetic resonance (MR) imaging, which is sensitive but not specific. Among the potential harms of false positive findings is lowered adherence to recommended surveillance post-therapy and by persons at increased cancer risk. Positron emission tomography (PET) plus computerized tomography (CT) is the molecular imaging modality most widely used in oncology. In up to 40% of cases, PET-CT leads to changes in therapeutic management. Newer PET tracers can detect tumor hypoxia, bone metastases in androgen-sensitive prostate cancer, and human epidermal growth factor receptor type 2 (HER2)-expressive tumors. Magnetic resonance spectroscopy provides insight into several metabolites at the same time. Combined with MRI, this yields magnetic resonance spectroscopic imaging (MRSI), which does not entail ionizing radiation and is thus suitable for repeated monitoring. Using advanced signal processing, quantitative information can be gleaned about molecular markers of brain, breast, prostate and other cancers. Radiation oncology has benefited from molecular imaging via PET-CT and MRSI. Advanced mathematical approaches can improve dose planning in stereotactic radiosurgery, stereotactic body radiotherapy and high dose-rate brachytherapy. Molecular imaging will likely impact profoundly on clinical decision making in oncology. Molecular imaging via MR could facilitate early detection especially in persons at high risk for specific cancers.

Related: Cancer Prevention and Risk Reduction
Department of Oncology/Pathology, Karolinska Institute, Stockholm, Sweden.


Elfström KM, Smelov V, Johansson AL, et al.
Long term duration of protective effect for HPV negative women: follow-up of primary HPV screening randomised controlled trial.
BMJ. 2014; 348:g130 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: To assess whether the increased sensitivity of screening for human papillomavirus (HPV) may represent overdiagnosis and to compare the long term duration of protective effect against cervical intraepithelial neoplasia grade 2 or worse (CIN2+) in HPV based and cytology based screening.
DESIGN: 13 year follow-up of the Swedescreen randomised controlled trial of primary HPV screening.
SETTING: Organised cervical screening programme in Sweden.
PARTICIPANTS: 12,527 women aged 32-38 attending organised screening were enrolled and randomised to HPV and cytology double testing (intervention arm, n=6257) or to cytology only, with samples frozen for future HPV testing (control arm, n=6270).
MAIN OUTCOME MEASURES: Cumulative incidence of CIN2+ and CIN3+ (Kaplan Meier curves). Longitudinal test characteristics were calculated for cytology only, HPV testing only, and cytology and HPV testing combined, adjusting for censoring.
RESULTS: The increased detection of CIN2+ in the intervention arm decreased over time. After six years, the cumulative incidence of CIN3+ was similar in both trial arms, and after 11 years the cumulative incidence of CIN2+ became similar in both arms. The longitudinal sensitivity of cytology for CIN2+ in the control arm at three years was similar to the sensitivity of HPV testing in the intervention arm at five years of follow-up: 85.94% (95% confidence interval 76.85% to 91.84%) v 86.40% (79.21% to 91.37%). The sensitivity of HPV screening for CIN3+after five years was 89.34% (80.10% to 94.58%) and for cytology after three years was 92.02% (80.59% to 96.97%).
CONCLUSIONS: Over long term follow-up, the cumulative incidence of CIN2+ was the same for HPV screening and for cytology, implying that the increased sensitivity of HPV screening for CIN2+ reflects earlier detection rather than overdiagnosis. The low long term risks of CIN3+ among women who tested negative in HPV screening, support screening intervals of five years for such women.
TRIAL REGISTRATION: Clinicaltrials.gov NCT00479375.

Related: Cervical Cancer Cervical Cancer Screening
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Box 281, 171 77 Stockholm, Sweden.


Strander B, Hällgren J, Sparén P
Effect of ageing on cervical or vaginal cancer in Swedish women previously treated for cervical intraepithelial neoplasia grade 3: population based cohort study of long term incidence and mortality.
BMJ. 2014; 348:f7361 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To determine factors influencing long term risks for acquiring or dying from invasive cervical or vaginal cancer in women previously treated for cervical intraepithelial neoplasia grade 3 (CIN3).
DESIGN: Population based cohort study conducted in 1958-2008, followed up until 2009 in the Swedish Cancer Registry and Swedish Cause of Death Register, linked to the Swedish Population Register. Standardised incidence and mortality ratios were calculated for the risk of acquiring or dying from vaginal or cervical cancer, with the general female population in Sweden as reference. Relative risks in multivariable regression models were also calculated, adjusting for follow-up duration, treatment period, and age at CIN3 treatment or attained age.
SETTING: Entire female population of Sweden.
PARTICIPANTS: 150,883 women in Sweden diagnosed and treated with CIN3 and followed up for invasive cervical or vaginal cancer, and related mortality. The cohort comprised 3,148,222 woman years.
MAIN OUTCOME MEASURES: Standardised incidence and mortality ratios, stratified by period for treatment. Relative standardised incidence ratios and standardised mortality ratios for age at acquiring or dying from cervical or vaginal cancer (attained age), adjusted for preset variables.
RESULTS: Women previously diagnosed with CIN3 had an increased risk of dying from invasive cervical or vaginal cancer, compared with the general female population (standardised mortality ratio 2.35, 95% confidence interval 2.11 to 2.61). After age 60 years, these women had an accelerated increased risk of acquiring invasive cancer; a similar steep increase in mortality risk was seen after age 70. Regression analyses indicated that the increase in risk over time is highly attributable to ageing.
CONCLUSIONS: Women previously treated for CIN3 are at increased risk of developing and dying from cervical or vaginal cancer, compared with the general female population. The risk accelerates above age 60 years, suggesting a need for lifelong surveillance of these women.

Related: Cervical Cancer Vaginal Cancer
Department of Obstetrics and Gynaecology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.


Kamposioras K, Anthoney A, Fernández Moro C, et al.
Impact of intrapancreatic or extrapancreatic bile duct involvement on survival following pancreatoduodenectomy for common bile duct cancer.
Br J Surg. 2014; 101(2):89-99 [PubMed] Related Publications
BACKGROUND: The clinicopathological factors that influence survival following pancreatoduodenectomy (PD) for common bile duct (CBD) cancer are not well known. This study aimed to investigate the effect of tumour involvement of the intrapancreatic versus extrapancreatic CBD on margin status, overall (OS) and disease-free (DFS) survival.
METHODS: This was a retrospective study of patients who underwent PD for CBD cancer between 2001 and 2009. Pathological examination was performed according to a previously described standardized protocol based on axial slicing. Clinicopathological data and outcome in terms of margin status, DFS and OS were compared between cancers involving exclusively the intrapancreatic CBD (CBDin) and those involving the extrapancreatic CBD, in isolation or combined with invasion of the intrapancreatic part of the duct (CBDex).
RESULTS: A total of 66 patients were enrolled. Most CBD cancers were locally advanced (97 per cent pathological (p) T3, 76 per cent pN1). Microscopic margin involvement (R1) was more frequent in CBDex than in CBDin cancers (34 of 39 versus 13 of 27; P = 0.001), more often multifocal (P < 0.001) and more frequently affected the periductal margin (P = 0.005). Venous resection was more often required for CBDex cancers (P = 0.009). CBDex cancers were associated with worse OS (median 21 versus 28 months; P = 0.020) and DFS (14 versus 31 months; P = 0.015), but the rate and site of recurrence did not differ. Metastasis to more than two lymph nodes was an independent predictor of OS and DFS.
CONCLUSION: CBDex cancer is associated with a higher rate of R1 resection and venous resection after PD, and has a worse outcome than CBDin cancer.

Related: Extra-Hepatic Bile duct cancer (cholangiocarcinoma)
Department of Oncology, St James's Institute of Oncology, Leeds, Sweden.


Peyrard-Janvid M, Leslie EJ, Kousa YA, et al.
Dominant mutations in GRHL3 cause Van der Woude Syndrome and disrupt oral periderm development.
Am J Hum Genet. 2014; 94(1):23-32 [PubMed] Article available free on PMC after 02/07/2014 Related Publications
Mutations in interferon regulatory factor 6 (IRF6) account for ∼70% of cases of Van der Woude syndrome (VWS), the most common syndromic form of cleft lip and palate. In 8 of 45 VWS-affected families lacking a mutation in IRF6, we found coding mutations in grainyhead-like 3 (GRHL3). According to a zebrafish-based assay, the disease-associated GRHL3 mutations abrogated periderm development and were consistent with a dominant-negative effect, in contrast to haploinsufficiency seen in most VWS cases caused by IRF6 mutations. In mouse, all embryos lacking Grhl3 exhibited abnormal oral periderm and 17% developed a cleft palate. Analysis of the oral phenotype of double heterozygote (Irf6(+/-);Grhl3(+/-)) murine embryos failed to detect epistasis between the two genes, suggesting that they function in separate but convergent pathways during palatogenesis. Taken together, our data demonstrated that mutations in two genes, IRF6 and GRHL3, can lead to nearly identical phenotypes of orofacial cleft. They supported the hypotheses that both genes are essential for the presence of a functional oral periderm and that failure of this process contributes to VWS.
Department of Biosciences and Nutrition, Karolinska Institutet, and Center for Biotechnology, 14183 Huddinge, Sweden. Electronic address:
Research funded by:
  • NIAMS NIH HHS
  • NIDCR NIH HHS
  • NIGMS NIH HHS
  • NIAMS NIH HHS


Heldin CH
Targeting the PDGF signaling pathway in tumor treatment.
Cell Commun Signal. 2013; 11:97 [PubMed] Article available free on PMC after 02/07/2014 Related Publications
Platelet-derived growth factor (PDGF) isoforms and PDGF receptors have important functions in the regulation of growth and survival of certain cell types during embryonal development and e.g. tissue repair in the adult. Overactivity of PDGF receptor signaling, by overexpression or mutational events, may drive tumor cell growth. In addition, pericytes of the vasculature and fibroblasts and myofibroblasts of the stroma of solid tumors express PDGF receptors, and PDGF stimulation of such cells promotes tumorigenesis. Inhibition of PDGF receptor signaling has proven to useful for the treatment of patients with certain rare tumors. Whether treatment with PDGF/PDGF receptor antagonists will be beneficial for more common malignancies is the subject for ongoing studies.

Related: Angiogenesis Inhibitors Cancer Prevention and Risk Reduction Signal Transduction
Ludwig Institute for Cancer Research, Science for life laboratory, Uppsala University, Box 595SE-751 24 Uppsala, Sweden.


Lundorff L, Sjøgren P, Hansen OB, et al.
Switching from high doses of pure μ-opioid agonists to transdermal buprenorphine in patients with cancer: a feasibility study.
J Opioid Manag. 2013 Jul-Aug; 9(4):255-62 [PubMed] Related Publications
BACKGROUND: Several myths on buprenorphine's pharmacology exist: possible analgesic ceiling effect, feasibility of combination with other opioid agonists, and the reversibility of side effects. Aim to evaluate: 1) if cancer patients receiving high doses of pure agonists could obtain adequate pain relief after switching to transdermal (TD) buprenorphine and 2) whether the numbers of breakthrough pain episodes after switching increased and whether they could be treated with the same doses of pure agonist as before switching.
DESIGN: The prospective open multicenter study included outpatients with moderate-to-severe cancer pain satisfactorily controlled.
SETTING: Patients were switched from the usual pure agonist to TD buprenorphine and were titrated to a stable dose. The assessments were: 1) daily self-assessment of pain intensity, numbers of rescue medications, and pain interference with sleep; 2) brief pain inventory; 3) pain relief and pain intensity; 4) quality of life; and 5) adverse events and symptoms.
RESULTS: Eighteen patients receiving 150-516 mg of morphine/day were included. The buprenorphine dose at the end of the study varied between 52.5 and 140 μg/h. No difference in pain before and after switching was shown. The level of rescue doses was maintained. The patches were well tolerated. A significant decrease in fatigue and an increase in global health status were seen after the switch.
CONCLUSION: It is feasible to switch cancer patients from high doses of pure μ-opioid agonists to TD buprenorphine without eliciting any antagonist effects, but the dose conversion factor is individual and the switching process should be tailored for the individual patient.

Related: Cancer Prevention and Risk Reduction
Consultant, Department of Palliative Care, Herning, Denmark; Department of Palliative Care, Uddevalla, Sweden.


Stemme S, Ghaderi M, Carlson JW
Diagnosis of endometrial stromal tumors: a clinicopathologic study of 25 biopsy specimens with identification of problematic areas.
Am J Clin Pathol. 2014; 141(1):133-9 [PubMed] Related Publications
OBJECTIVES: To assess the difficulties associated with diagnosing endometrial stromal tumors (ESTs) on endometrial biopsy.
METHODS: We examined 25 endometrial biopsy specimens from 19 consecutive women diagnosed with either endometrial stromal nodule (n = 3) or endometrial stromal sarcoma (n = 16).
RESULTS: Rereview of the biopsy specimens revealed a stromal fragment suspicious for an EST in 16, of which eight had received a benign diagnosis on initial review. Most ESTs had an aglandular stromal fragment that was 5 mm or larger. Stromal fragments of this size were not encountered in the control material. Problematic areas included highly cellular leiomyoma and a lack of attention to the stromal compartment.
CONCLUSIONS: Most endometrial stromal tumors present with large aglandular stromal fragments (≥5 mm). These fragments are large enough that difficulties in diagnosis appear to be due to a lack of attention to the stromal compartment.

Related: Endometrial (Uterus) Cancer Endometrial Cancer
Institution for Oncology-Pathology, Cancer Centrum Karolinska R8:05, Karolinska Institutet, Stockholm, Sweden, 17176; e-mail:


Mavroidis P, Milickovic N, Cruz WF, et al.
Comparison of different fractionation schedules toward a single fraction in high-dose-rate brachytherapy as monotherapy for low-risk prostate cancer using 3-dimensional radiobiological models.
Int J Radiat Oncol Biol Phys. 2014; 88(1):216-23 [PubMed] Related Publications
PURPOSE: The aim of the present study was the investigation of different fractionation schemes to estimate their clinical impact. For this purpose, widely applied radiobiological models and dosimetric measures were used to associate their results with clinical findings.
METHODS AND MATERIALS: The dose distributions of 12 clinical high-dose-rate brachytherapy implants for prostate were evaluated in relation to different fractionation schemes. The fractionation schemes compared were: (1) 1 fraction of 20 Gy; (2) 2 fractions of 14 Gy; (3) 3 fractions of 11 Gy; and (4) 4 fractions of 9.5 Gy. The clinical effectiveness of the different fractionation schemes was estimated through the complication-free tumor control probability (P+), the biologically effective uniform dose, and the generalized equivalent uniform dose index.
RESULTS: For the different fractionation schemes, the tumor control probabilities were 98.5% in 1×20 Gy, 98.6% in 2×14 Gy, 97.5% in 3×11 Gy, and 97.8% in 4×9.5 Gy. The corresponding P+ values were 88.8% in 1×20 Gy, 83.9% in 2×14 Gy, 86.0% in 3×11 Gy, and 82.3% in 4×9.5 Gy. With use of the fractionation scheme 4×9.5 Gy as reference, the isoeffective schemes regarding tumor control for 1, 2, and 3 fractions were 1×19.68 Gy, 2×13.75 Gy, and 3×11.05 Gy. The optimum fractionation schemes for 1, 2, 3, and 4 fractions were 1×19.16 Gy with a P+ of 91.8%, 2×13.2 Gy with a P+ of 89.6%, 3×10.6 Gy with a P+ of 88.4%, and 4×9.02 Gy with a P+ of 86.9%.
CONCLUSIONS: Among the fractionation schemes 1×20 Gy, 2×14 Gy, 3×11 Gy, and 4×9.5 Gy, the first scheme was more effective in terms of P+. After performance of a radiobiological optimization, it was shown that a single fraction of 19.2 to 19.7 Gy (average 19.5 Gy) should produce at least the same benefit as that given by the 4×9.5 Gy scheme, and it should reduce the expected total complication probability by approximately 40% to 55%.

Related: Brachytherapy Prostate Cancer
Department of Radiation Oncology, University of Texas Health Sciences Center, San Antonio, Texas; Department of Medical Radiation Physics, Karolinska Institutet and Stockholm University, Stockholm, Sweden. Electronic address:


Butts C, Socinski MA, Mitchell PL, et al.
Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial.
Lancet Oncol. 2014; 15(1):59-68 [PubMed] Related Publications
BACKGROUND: Effective maintenance therapies after chemoradiotherapy for lung cancer are lacking. Our aim was to investigate whether the MUC1 antigen-specific cancer immunotherapy tecemotide improves survival in patients with stage III unresectable non-small-cell lung cancer when given as maintenance therapy after chemoradiation.
METHODS: The phase 3 START trial was an international, randomised, double-blind trial that recruited patients with unresectable stage III non-small-cell lung cancer who had completed chemoradiotherapy within the 4-12 week window before randomisation and received confirmation of stable disease or objective response. Patients were stratified by stage (IIIA vs IIIB), response to chemoradiotherapy (stable disease vs objective response), delivery of chemoradiotherapy (concurrent vs sequential), and region using block randomisation, and were randomly assigned (2:1, double-blind) by a central interactive voice randomisation system to either tecemotide or placebo. Injections of tecemotide (806 μg lipopeptide) or placebo were given every week for 8 weeks, and then every 6 weeks until disease progression or withdrawal. Cyclophosphamide 300 mg/m(2) (before tecemotide) or saline (before placebo) was given once before the first study drug administration. The primary endpoint was overall survival in a modified intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00409188.
FINDINGS: From Feb 22, 2007, to Nov 15, 2011, 1513 patients were randomly assigned (1006 to tecemotide and 507 to placebo). 274 patients were excluded from the primary analysis population as a result of a clinical hold, resulting in analysis of 829 patients in the tecemotide group and 410 in the placebo group in the modified intention-to-treat population. Median overall survival was 25.6 months (95% CI 22.5-29.2) with tecemotide versus 22.3 months (19.6-25.5) with placebo (adjusted HR 0.88, 0.75-1.03; p=0.123). In the patients who received previous concurrent chemoradiotherapy, median overall survival for the 538 (65%) of 829 patients assigned to tecemotide was 30.8 months (95% CI 25.6-36.8) compared with 20.6 months (17.4-23.9) for the 268 (65%) of 410 patients assigned to placebo (adjusted HR 0.78, 0.64-0.95; p=0.016). In patients who received previous sequential chemoradiotherapy, overall survival did not differ between the 291 (35%) patients in the tecemotide group and the 142 (35%) patients in the placebo group (19.4 months [95% CI 17.6-23.1] vs 24.6 months [18.8-33.0], respectively; adjusted HR 1.12, 0.87-1.44; p=0.38). Grade 3-4 adverse events seen with a greater than 2% frequency with tecemotide were dyspnoea (49 [5%] of 1024 patients in the tecemotide group vs 21 [4%] of 477 patients in the placebo group), metastases to central nervous system (29 [3%] vs 6 [1%]), and pneumonia (23 [2%] vs 12 [3%]). Serious adverse events with a greater than 2% frequency with tecemotide were pneumonia (30 [3%] in the tecemotide group vs 14 [3%] in the placebo group), dyspnoea (29 [3%] vs 13 [3%]), and metastases to central nervous system (32 [3%] vs 9 [2%]). Serious immune-related adverse events did not differ between groups.
INTERPRETATION: We found no significant difference in overall survival with the administration of tecemotide after chemoradiotherapy compared with placebo for all patients with unresectable stage III non-small-cell lung cancer. However, tecemotide might have a role for patients who initially receive concurrent chemoradiotherapy, and further study in this population is warranted.
FUNDING: Merck KGaA (Darmstadt, Germany).

Related: Non-Small Cell Lung Cancer Lung Cancer
Cross Cancer Institute, Edmonton, AB, Canada. Electronic address:


Valind A, Jin Y, Baldetorp B, Gisselsson D
Whole chromosome gain does not in itself confer cancer-like chromosomal instability.
Proc Natl Acad Sci U S A. 2013; 110(52):21119-23 [PubMed] Article available free on PMC after 24/06/2014 Related Publications
Constitutional aneuploidy is typically caused by a single-event meiotic or early mitotic error. In contrast, somatic aneuploidy, found mainly in neoplastic tissue, is attributed to continuous chromosomal instability. More debated as a cause of aneuploidy is aneuploidy itself; that is, whether aneuploidy per se causes chromosomal instability, for example, in patients with inborn aneuploidy. We have addressed this issue by quantifying the level of somatic mosaicism, a proxy marker of chromosomal instability, in patients with constitutional aneuploidy by precise background-filtered dual-color FISH. In contrast to previous studies that used less precise methods, we find that constitutional trisomy, even for large chromosomes that are often trisomic in cancer, does not confer a significantly elevated rate of somatic chromosomal mosaicism in individual cases. Constitutional triploidy was associated with an increased level of somatic mosaicism, but this consisted mostly of reversion from trisomy to disomy and did not correspond to a proportionally elevated level of chromosome mis-segregation in triploids, indicating that the observed mosaicism resulted from a specific accumulation of cells with a hypotriploid chromosome number. In no case did the rate of somatic mosaicism in constitutional aneuploidy exceed that of "chromosomally stable" cancer cells. Our findings show that even though constitutional aneuploidy was in some cases associated with low-level somatic mosaicism, it was insufficient to generate the cancer-like levels expected if aneuploidy single-handedly triggered cancer-like chromosomal instability.

Related: FISH Cancer Prevention and Risk Reduction
Department of Clinical Genetics, Lund University, University and Regional Laboratories, Biomedical Center B13, Lund SE22184, Sweden.


Randén M, Runesdotter S, Strang P
Cancer treatment of severely-III patients not eligible for chemotherapy.
Anticancer Res. 2013; 33(12):5639-43 [PubMed] Related Publications
BACKGROUND: Despite having disseminated cancer, not all patients are eligible for palliative chemotherapy or targeted therapies. Aim: To study reasons for withholding palliative chemotherapy, to survey which alternatives were offered and to study survival outcomes.
MATERIALS AND METHODS: Medical records of 346 patients with disseminated cancer were collected. Univariate and multivariate statistics were applied.
RESULTS: In total, 48% (n=164) of patients were not offered palliative chemotherapy, mainly depending on diagnosis, age and performance status. Instead, palliative radiotherapy (44%) or endocrine treatments (25%) (breast and prostate cancer) were prescribed. The mean survival for these patients was 216 days, with median survival of only 77 days. In the Cox multivariate analysis survival, prospects were better if the patient was ambulatory and living at home at the first consultation (p<0.01), if performance status was acceptable (p<0.01) and if endocrine treatment was an option (p<0.05).
CONCLUSION: The prognosis is quite variable, even in cases where palliative chemotherapy is not an option. A hormone-sensitive tumour and a good performance status are significant factors affecting survival in this patient group.

Related: Cancer Prevention and Risk Reduction
Stockholms Sjukhem, P.O. Box 12230, 102 26 Stockholm, Sweden.


Rubio CA, Jaramillo E
Advanced microtubular colorectal adenomas: a 10-year survey at a single hospital.
Anticancer Res. 2013; 33(12):5471-6 [PubMed] Related Publications
BACKGROUND: Colorectal carcinoma, the third most commonly diagnosed type of cancer in Europe and the USA, usually originates from colorectal adenoma (CRA). Three main histological phenotypes of CRA are usually recognized: tubular, villous and traditional serrated (TA, VA and TSA, respectively). In 1997, we reported a novel histological phenotype, the microtubular adenoma (MTA), epitomized by dysplastic epithelium arranged in closed rings (microtubules), with sideways-elongated outgrowth.
MATERIALS AND METHODS: The material includes 4,446 CRAs diagnosed at our Department during a 10-year period (2001-2010).
RESULTS: Out of 4,446 CRAs, 68 (1.5%) were MTA; of these, 38 (55.9%) exhibited low-grade dysplasia (LGD), 17 (25.0%), high-grade-dysplasia, two (2.9%) intraepithelial carcinoma and three (4.4%), intramucosal carcinoma. Out of the 68 MTA, 22 (32.3%) were advanced MTA. Submucosal carcinoma (SMC) was present in eight (11.8%) MTAs. Ninety-four per cent (64/68) of the MTAs were left-sided adenomas. In previous work, we found that cell proliferation occurred in the dysplastic microtubules in MTA, initially in the luminal dysplastic epithelium in TA and VA, and initially at the bottom of the serrated dysplastic crypts in TSA.
CONCLUSION: Due to these distinctive microscopic and cell proliferative attributes, a predominant left-sided location and the absence of serrated configurations, it is submitted that MTA is a specific CRA phenotype, at variance with TA, VA, and TSA. The high frequency of SMC strongly suggests that MTA is an important alternative pathway in colorectal carcinogenesis.

Related: Colorectal (Bowel) Cancer USA
Gastrointestinal and Liver Pathology Research Laboratory, Department of Pathology, Karolinska Institute and University Hospital, 17176, Stockholm, Sweden.


Kopparapu PK, Boorjian SA, Robinson BD, et al.
Expression of cyclin d1 and its association with disease characteristics in bladder cancer.
Anticancer Res. 2013; 33(12):5235-42 [PubMed] Related Publications
AIM: Invasive urothelial carcinoma of the bladder (UCB) is characterized by alterations in cell-cycle regulatory pathways. Defects in the expression of cyclin D1, a key cell-cycle regulator, have been implicated in progression of various types of cancer. In the present study, we investigated whether cyclin D1 expression is associated with clinicopathological parameters and whether it has any potential prognostic value in determining risk of UCB recurrence.
PATIENTS AND METHODS: Tissue microarrays containing bladder cancer specimens (n=212) and adjacent normal bladder tissues (n=131) were immunostained using an antibody against cyclin D1. The association between cyclin D1 and clinicopathological parameters including stage, lymph node metastasis, and disease-free survival, were evaluated. Cyclin D1 mRNA expression data from human normal bladder (n=14) and cancer specimens (n=28) were extracted from the public Oncomine database.
RESULTS: Cyclin D1 mRNA and protein expression were significantly higher in UCB compared to adjacent non-malignant bladder tissue (for mRNA p=0.003, for protein p=0.001). Cyclin D1 protein expression was significantly higher in non-invasive tumors than in muscle-invasive UCB (p=0.016). Among patients with muscle-invasive UCB, increased cyclin D1 expression in tumor cells significantly correlated with lymph node metastasis (p<0.001), and there was a trend of cyclin D1 together with lymph node positivity to be associated with disease recurrence (p=0.678). Loss of nuclear cyclin D1 expression in tumor cells was likewise significantly associated with the presence of lymph node metastasis (p<0.001).
CONCLUSION: Altered expression of cyclin D1 is associated with lymph node metastasis and risk of UCB recurrence. Cyclin D1 expression may therefore have clinical value as a prognostic marker and potential therapeutic target.

Related: Bladder Cancer Bladder Cancer - Molecular Biology
Division of Experimental Cancer Research, Department of Laboratory Medicine in Malmö, Lund University, Clinical Research Center, 205 02, Malmö, Sweden. Tel: +46 40391106,


Michaelson MD, Oudard S, Ou YC, et al.
Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer.
J Clin Oncol. 2014; 32(2):76-82 [PubMed] Related Publications
PURPOSE: We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC).
PATIENTS AND METHODS: Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned.
RESULTS: Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%).
CONCLUSION: The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.

Related: Prostate Cancer Sunitinib (Sutent) Docetaxel
M. Dror Michaelson, Massachusetts General Hospital Cancer Center, Boston, MA; Stephane Oudard, George Pompidou European Hospital, Rene Descartes University, Paris; Nadine Houede, Institut Bergonie, Bordeaux; Tristan Maurina, CHU de Besançon, Hôpital Jean Minjoz, Besançon, France; Yen...


Kyrø C, Olsen A, Landberg R, et al.
Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer.
J Natl Cancer Inst. 2014; 106(1):djt352 [PubMed] Article available free on PMC after 24/06/2014 Related Publications
BACKGROUND: Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations.
METHODS: The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored.
RESULTS: High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher).
CONCLUSIONS: High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.

Related: Colorectal (Bowel) Cancer
Affiliations of authors: Danish Cancer Society Research Center, Copenhagen, Denmark (CK, AO, JC, AT); Department of Food Science, BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden (RL, PÅ); Department of Community Medicine, University of Tromsø, Tromsø, Norway (...
Research funded by:


Greenhalf W, Ghaneh P, Neoptolemos JP, et al.
Pancreatic cancer hENT1 expression and survival from gemcitabine in patients from the ESPAC-3 trial.
J Natl Cancer Inst. 2014; 106(1):djt347 [PubMed] Related Publications
BACKGROUND: Human equilibrative nucleoside transporter 1 (hENT1) levels in pancreatic adenocarcinoma may predict survival in patients who receive adjuvant gemcitabine after resection.
METHODS: Microarrays from 434 patients randomized to chemotherapy in the ESPAC-3 trial (plus controls from ESPAC-1/3) were stained with the 10D7G2 anti-hENT1 antibody. Patients were classified as having high hENT1 expression if the mean H score for their cores was above the overall median H score (48). High and low hENT1-expressing groups were compared using Kaplan-Meier curves, log-rank tests, and Cox proportional hazards models. All statistical tests were two-sided.
RESULTS: Three hundred eighty patients (87.6%) and 1808 cores were suitable and included in the final analysis. Median overall survival for gemcitabine-treated patients (n = 176) was 23.4 (95% confidence interval [CI] = 18.3 to 26.0) months vs 23.5 (95% CI = 19.8 to 27.3) months for 176 patients treated with 5-fluorouracil/folinic acid (χ(2) 1=0.24; P = .62). Median survival for patients treated with gemcitabine was 17.1 (95% CI = 14.3 to 23.8) months for those with low hENT1 expression vs 26.2 (95% CI = 21.2 to 31.4) months for those with high hENT1 expression (χ(2)₁= 9.87; P = .002). For the 5-fluorouracil group, median survival was 25.6 (95% CI = 20.1 to 27.9) and 21.9 (95% CI = 16.0 to 28.3) months for those with low and high hENT1 expression, respectively (χ(2)₁ = 0.83; P = .36). hENT1 levels were not predictive of survival for the 28 patients of the observation group (χ(2)₁ = 0.37; P = .54). Multivariable analysis confirmed hENT1 expression as a predictive marker in gemcitabine-treated (Wald χ(2) = 9.16; P = .003) but not 5-fluorouracil-treated (Wald χ(2) = 1.22; P = .27) patients.
CONCLUSIONS: Subject to prospective validation, gemcitabine should not be used for patients with low tumor hENT1 expression.

Related: Fluorouracil Leucovorin Cancer of the Pancreas Pancreatic Cancer Gemcitabine
Affiliations of authors: Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK (WG, JPN, EG, TFC, PG, EC, CMH, CLR, FC, RJ); the Princess Margaret Hospital, Toronto, Canada (MJM); Manchester Academic Health Sciences Centre, Chri...
Research funded by:


Low HP, Tiwari A, Janjanam J, et al.
Screening preeclamptic cord plasma for proteins associated with decreased breast cancer susceptibility.
Genomics Proteomics Bioinformatics. 2013; 11(6):335-44 [PubMed] Related Publications
Preeclampsia, a complication of pregnancy characterized by hypertension and proteinuria, has been found to reduce the subsequent risk for breast cancer in female offspring. As this protective effect could be due to exposure to preeclampsia-specific proteins during intrauterine life, the proteomic profiles of umbilical cord blood plasma between preeclamptic and normotensive pregnancies were compared. Umbilical cord plasma samples, depleted of 14 abundant proteins, were subjected to proteomic analysis using the quantitative method of nanoACQUITY ultra performance liquid chromatography-mass spectrometry with elevated energy mode of acquisition(E) (NanoUPLC-MS(E)). Sixty-nine differentially expressed proteins were identified, of which 15 and 6 proteins were only detected in preeclamptic and normotensive pregnancies, respectively. Additionally, expression of 8 proteins (gelsolin, complement C5, keratin type I cytoskeletal 10, pigment epithelium-derived factor, complement factor B, complement component C7, hemoglobin subunit gamma-2 and alpha-fetoprotein) were up-regulated in preeclampsia with a fold change of ≥2.0 when compared to normotensive pregnancies. The identification of alpha-fetoprotein in preeclamptic umbilical cord blood plasma supported the validity of this screen as alpha-fetoprotein has anti-estrogenic properties and has previously been linked to preeclampsia as well as a reduced breast cancer risk. The findings of this pilot study may provide new insights into the mechanistic link between preeclampsia and potentially reduced breast cancer susceptibility in adult life.

Related: Breast Cancer
Department of Cancer Biology, University of Massachusetts Medical School, Worcester, MA 01605, USA.
Research funded by:


Speedy HE, Di Bernardo MC, Sava GP, et al.
A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia.
Nat Genet. 2014; 46(1):56-60 [PubMed] Related Publications
Genome-wide association studies (GWAS) of chronic lymphocytic leukemia (CLL) have shown that common genetic variation contributes to the heritable risk of CLL. To identify additional CLL susceptibility loci, we conducted a GWAS and performed a meta-analysis with a published GWAS totaling 1,739 individuals with CLL (cases) and 5,199 controls with validation in an additional 1,144 cases and 3,151 controls. A combined analysis identified new susceptibility loci mapping to 3q26.2 (rs10936599, P = 1.74 × 10(-9)), 4q26 (rs6858698, P = 3.07 × 10(-9)), 6q25.2 (IPCEF1, rs2236256, P = 1.50 × 10(-10)) and 7q31.33 (POT1, rs17246404, P = 3.40 × 10(-8)). Additionally, we identified a promising association at 5p15.33 (CLPTM1L, rs31490, P = 1.72 × 10(-7)) and validated recently reported putative associations at 5p15.33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL.

Related: Chromosome 3 Chronic Lymphocytic Leukemia (CLL) CLL - Molecular Biology
1] Division of Genetics and Epidemiology, Institute of Cancer Research, Sutton, Surrey, UK. [2].
Research funded by:


Taylor FG, Quirke P, Heald RJ, et al.
Preoperative magnetic resonance imaging assessment of circumferential resection margin predicts disease-free survival and local recurrence: 5-year follow-up results of the MERCURY study.
J Clin Oncol. 2014; 32(1):34-43 [PubMed] Related Publications
PURPOSE: The prognostic relevance of preoperative high-resolution magnetic resonance imaging (MRI) assessment of circumferential resection margin (CRM) involvement is unknown. This follow-up study of 374 patients with rectal cancer reports the relationship between preoperative MRI assessment of CRM staging, American Joint Committee on Cancer (AJCC) TNM stage, and clinical variables with overall survival (OS), disease-free survival (DFS), and time to local recurrence (LR).
PATIENTS AND METHODS: Patients underwent protocol high-resolution pelvic MRI. Tumor distance to the mesorectal fascia of ≤ 1 mm was recorded as an MRI-involved CRM. A Cox proportional hazards model was used in multivariate analysis to determine the relationship of MRI assessment of CRM to survivorship after adjusting for preoperative covariates.
RESULTS: Surviving patients were followed for a median of 62 months. The 5-year OS was 62.2% in patients with MRI-clear CRM compared with 42.2% in patients with MRI-involved CRM with a hazard ratio (HR) of 1.97 (95% CI, 1.27 to 3.04; P < .01). The 5-year DFS was 67.2% (95% CI, 61.4% to 73%) for MRI-clear CRM compared with 47.3% (95% CI, 33.7% to 60.9%) for MRI-involved CRM with an HR of 1.65 (95% CI, 1.01 to 2.69; P < .05). Local recurrence HR for MRI-involved CRM was 3.50 (95% CI, 1.53 to 8.00; P < .05). MRI-involved CRM was the only preoperative staging parameter that remained significant for OS, DFS, and LR on multivariate analysis.
CONCLUSION: High-resolution MRI preoperative assessment of CRM status is superior to AJCC TNM-based criteria for assessing risk of LR, DFS, and OS. Furthermore, MRI CRM involvement is significantly associated with distant metastatic disease; therefore, colorectal cancer teams could intensify treatment and follow-up accordingly to improve survival outcomes.
Fiona G.M. Taylor and Ian R. Swift, Mayday University Hospital, Croydon; Gina Brown, The Royal Marsden National Health Service (NHS) Foundation Trust, Sutton, Surrey; Philip Quirke, Leeds Institute of Molecular Medicine, University of Leeds; David Sebag-Montefiore, St James's Institute of Oncology ...


Gojon H, Fawunmi D, Valachis A
Sentinel lymph node biopsy in patients with microinvasive breast cancer: a systematic review and meta-analysis.
Eur J Surg Oncol. 2014; 40(1):5-11 [PubMed] Related Publications
BACKGROUND: The aim of this meta-analysis is to evaluate the role of sentinel lymph node biopsy (SLNB) in patients with microinvasive breast cancer.
METHODS: We searched MEDLINE and ISI Web of Science to identify studies including patients with microinvasive breast cancer who underwent SLNB and reported the rate of sentinel-node positivity. We performed proportion meta-analysis using either fixed or random-effects model based on the between-study heterogeneity.
FINDINGS: A total of 24 studies including 968 patients met the eligibility criteria. The summary estimate for the sentinel-node (SN) positivity rate was 3.2% (95% Confidence Interval (CI): 2.1%-4.6%), 4.0% (95% CI 2.7%-5.5%), and 2.9% (95% CI: 1.6%-4.6%) for macrometastasis, micrometastasis and isolated tumor cells (ITC) respectively. Significant between-study heterogeneity was observed only in the meta-analysis of ITC positivity rate.
INTERPRETATION: The amount of positive sentinel node in patients with proven microinvasive breast cancer is relatively low. As a result, the indications for SLNB in these patients should be probably individualized.

Related: Breast Cancer
Department of Oncology, Karolinska Solna, 171 76 Stockholm, Sweden.


Hajiebrahimi M, Bahmanyar S, Öberg S, et al.
Breast cancer risk in opposite-sexed twins: influence of birth weight and co-twin birth weight.
J Natl Cancer Inst. 2013; 105(23):1833-6 [PubMed] Related Publications
Most, but not all, studies report a positive association between birth weight, as an indirect marker of prenatal hormone exposure, and offspring breast cancer risk, particularly premenopausal breast cancer. Females from opposite-sexed twin pairs may also be prenatally exposed to androgens from their twin brothers. A Swedish study of opposite-sexed twins with a small sample size found a very strong positive association between female birth weight and breast cancer risk. In this case-control study, nested within a cohort of female opposite-sexed twins, we included 543 breast cancer case subjects diagnosed in the period from 1972 to 2008 and 2715 matched control subjects. Conditional logistic regression estimated the breast cancer risk associated with birth weight and other birth characteristics, including gestational age and co-twin birth weight. All statistical tests were two-sided. There was no association between birth weight (odds ratio = 1.01; 95% confidence interval = 0.70 to 1.46) or twin brother's birth weight and risk of breast cancer, which suggests the previously reported strong positive association may have been a chance finding.

Related: Breast Cancer
Affiliations of authors: Clinical Epidemiology Unit, Department of Medicine (MH, SB, SC), Center for Pharmacoepidemiology, Department of Medicine (SB), and Department of Medical Epidemiology and Biostatistics (ANI), Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard Schoo...


Dimberg J, Hong TT, Skarstedt M, et al.
Detection of cytomegalovirus DNA in colorectal tissue from Swedish and Vietnamese patients with colorectal cancer.
Anticancer Res. 2013; 33(11):4947-50 [PubMed] Related Publications
BACKGROUND: Human cytomegalovirus (HCMV) has been implicated as a factor, which might be associated with colorectal cancer (CRC) progression. Data from studies with HCMV-infected tumour cell lines have highlighted an oncomodulatory potential of HCMV. In the present study, we aimed to evaluate the prevalence of HCMV DNA in CRC tissue compared to matched normal tissue, and its association with clinical factors.
PATIENTS AND METHODS: We used quantitative real-time polymerase chain reaction assay to detect HCMV DNA in 202 cancerous and paired normal tissue from Swedish (n=119) and Vietnamese (n=83) CRC patients.
RESULTS: Overall, the HCMV DNA rate was significantly higher in cancerous in relation to paired normal tissue. Furthermore, a significantly higher frequency (39.8%) of HCMV DNA was observed in cancer tissues from the Vietnamese patients compared to the Swedish patients (15.1%). The prevalence of HCMV DNA in CRC tissue of 50% of those with disseminated disease tended to be higher compared to those with localized disease, with a prevalence of 33.3% in Vietnamese patients.
CONCLUSION: Our observations indicate that the prevalence of HCMV DNA differs significantly between cancer and matched normal tissues. Thus, these data support a possible role of CMV in CRC. Moreover, we noted differences between Swedish and Vietnamese patients, indicating a role of ethnicity.

Related: Colorectal (Bowel) Cancer
Department of Laboratory Services, Ryhov County Hospital, SE-551 85 Jönköping, Sweden.


Poplin E, Wasan H, Rolfe L, et al.
Randomized, multicenter, phase II study of CO-101 versus gemcitabine in patients with metastatic pancreatic ductal adenocarcinoma: including a prospective evaluation of the role of hENT1 in gemcitabine or CO-101 sensitivity.
J Clin Oncol. 2013; 31(35):4453-61 [PubMed] Related Publications
PURPOSE: Gemcitabine requires transporter proteins to cross cell membranes. Low expression of human equilibrative nucleoside transporter-1 (hENT1) may result in gemcitabine resistance in pancreatic ductal adenocarcinoma (PDAC). CO-101, a lipid-drug conjugate of gemcitabine, was rationally designed to enter cells independently of hENT1. We conducted a randomized controlled trial to determine whether CO-101 improved survival versus gemcitabine in patients with metastatic PDAC (mPDAC) with low hENT1. The study also tested the hypothesis that gemcitabine is more active in patients with mPDAC tumors with high versus low hENT1 expression.
PATIENTS AND METHODS: Patients were randomly assigned to CO-101 or gemcitabine, after providing a metastasis sample for blinded hENT1 assessment. An immunohistochemistry test measuring tumor hENT1 was developed. To dichotomize the population, an hENT1 cutoff value was defined using primary PDAC samples from an adjuvant trial, and a high/low cutoff was applied. The primary end point was overall survival (OS) in the low hENT1 subgroup.
RESULTS: Of 367 patients enrolled, hENT1 status was measured in 358 patients (97.5%). Two hundred thirty-two (64.8%) of 358 patients were hENT1 low. There was no difference in OS between treatments in the low hENT1 subgroup or overall, with hazard ratios (HRs) of 0.994 (95% CI, 0.746 to 1.326) and 1.072 (95% CI, 0.856 to 1.344), respectively. The toxicity profiles in both arms were similar. Within the gemcitabine arm, there was no difference in survival between the high and low hENT1 subgroups (HR, 1.147; 95% CI, 0.809 to 1.626).
CONCLUSION: CO-101 is not superior to gemcitabine in patients with mPDAC and low tumor hENT1. Metastasis hENT1 expression did not predict gemcitabine outcome.

Related: Cancer of the Pancreas Pancreatic Cancer Gemcitabine
Elizabeth Poplin, Cancer Institute of New Jersey, New Brunswick, NJ; Mitch Raponi, Elaina Mann, Cynthia Voong, and Andrew Allen, Clovis Oncology, San Francisco, CA; Hejin Hahn and Vince Picozzi, Virginia Mason Medical Center, Seattle, WA; Adam Dicker, Radiation Therapy Oncology Group, Philadelphia,...
Research funded by:


Ekström J, Mühr LS, Bzhalava D, et al.
Diversity of human papillomaviruses in skin lesions.
Virology. 2013; 447(1-2):300-11 [PubMed] Related Publications
Pools of frozen biopsies from patients with squamous cell carcinoma (SCC) (n=29) actinic keratosis (AK) (n=31), keratoacanthoma (n=91) and swab samples from 84 SCCs and 91 AKs were analysed with an extended HPV general primer PCR and high-throughput sequencing of amplimers. We found 273 different HPV isolates (87 known HPV types, 139 previously known HPV sequences (putative types) and 47 sequences from novel putative HPV types). Among the new sequences, five clustered in genus Betapapillomavirus and 42 in genus Gammapapillomavirus. Resequencing of the three pools between 21 to 70 times resulted in the detection of 283 different known or putative HPV types, with 156 different sequences found in only one of the pools. Type-specific PCRs for 37 putative types from an additional 296 patients found only two of these putative types. In conclusion, skin lesions contain a large diversity of HPV types, but most appeared to be rare infections.

Related: Skin Cancer
Department of Laboratory Medicine, Lund University, SE 20502 Malmö, Sweden; Departments of Laboratory Medicine, Medical Epidemiology & Biostatistics, Karolinska Institutet and Departments of Clinical Microbiology and Pathology, Karolinska Hospital, Stockholm, Sweden.


Ronco G, Dillner J, Elfström KM, et al.
Efficacy of HPV-based screening for prevention of invasive cervical cancer: follow-up of four European randomised controlled trials.
Lancet. 2014; 383(9916):524-32 [PubMed] Related Publications
BACKGROUND: In four randomised trials, human papillomavirus (HPV)-based screening for cervical cancer was compared with cytology-based cervical screening, and precursors of cancer were the endpoint in every trial. However, direct estimates are missing of the relative efficacy of HPV-based versus cytology-based screening for prevention of invasive cancer in women who undergo regular screening, of modifiers (eg, age) of this relative efficacy, and of the duration of protection. We did a follow-up study of the four randomised trials to investigate these outcomes.
METHODS: 176,464 women aged 20-64 years were randomly assigned to HPV-based (experimental arm) or cytology-based (control arm) screening in Sweden (Swedescreen), the Netherlands (POBASCAM), England (ARTISTIC), and Italy (NTCC). We followed up these women for a median of 6·5 years (1,214,415 person-years) and identified 107 invasive cervical carcinomas by linkage with screening, pathology, and cancer registries, by masked review of histological specimens, or from reports. Cumulative and study-adjusted rate ratios (experimental vs control) were calculated for incidence of invasive cervical carcinoma.
FINDINGS: The rate ratio for invasive cervical carcinoma among all women from recruitment to end of follow-up was 0·60 (95% CI 0·40-0·89), with no heterogeneity between studies (p=0·52). Detection of invasive cervical carcinoma was similar between screening methods during the first 2·5 years of follow-up (0·79, 0·46-1·36) but was significantly lower in the experimental arm thereafter (0·45, 0·25-0·81). In women with a negative screening test at entry, the rate ratio was 0·30 (0·15-0·60). The cumulative incidence of invasive cervical carcinoma in women with negative entry tests was 4·6 per 10(5) (1·1-12·1) and 8·7 per 10(5) (3·3-18·6) at 3·5 and 5·5 years, respectively, in the experimental arm, and 15·4 per 10(5) (7·9-27·0) and 36·0 per 10(5) (23·2-53·5), respectively, in the control arm. Rate ratios did not differ by cancer stage, but were lower for adenocarcinoma (0·31, 0·14-0·69) than for squamous-cell carcinoma (0·78, 0·49-1·25). The rate ratio was lowest in women aged 30-34 years (0·36, 0·14-0·94).
INTERPRETATION: HPV-based screening provides 60-70% greater protection against invasive cervical carcinomas compared with cytology. Data of large-scale randomised trials support initiation of HPV-based screening from age 30 years and extension of screening intervals to at least 5 years.
FUNDING: European Union, Belgian Foundation Against Cancer, KCE-Centre d'Expertise, IARC, The Netherlands Organisation for Health Research and Development, the Italian Ministry of Health.

Related: Cancer Screening and Early Detection Cervical Cancer
Center for Cancer Epidemiology and Prevention, AO City of Health and Science, Turin, Italy. Electronic address:


Högberg C, Karling P, Rutegård J, et al.
Immunochemical faecal occult blood tests in primary care and the risk of delay in the diagnosis of colorectal cancer.
Scand J Prim Health Care. 2013; 31(4):209-14 [PubMed] Article available free on PMC after 24/06/2014 Related Publications
OBJECTIVE: To evaluate the value, risks, and shortcomings of immunochemical faecal occult blood tests (iFOBTs) in the diagnosis of colorectal cancer (CRC) and adenomas with high-grade dysplasia (HGD) in patients initially presenting to primary care.
DESIGN: A retrospective population-based study.
SETTING AND SUBJECTS: All 495 cases of CRC and adenomas with HGD diagnosed in the county of Jämtland, Sweden from 2005 to 2009.
RESULTS: Of 495 patients 323 (65%) initially presented to primary care. IFOBTs were performed in 215 of 323 (67%) patients. The sensitivity of iFOBT for CRC and adenomas with HGD was 88% (83% when patients with a history of rectal bleeding were excluded). Of 34 patients with anaemia found en passant, 10 had negative iFOBTs. Time to diagnosis was longer for patients with negative iFOBTs (p < 0.0005).
CONCLUSION: IFOBT might be helpful in selecting which patients to refer for colonoscopy. However, iFOBT has a limited sensitivity as a diagnostic test for CRC and adenomas with HGD. Relying only on iFOBT for colonoscopy referral could delay diagnosis, especially for patients with anaemia found en passant.

Related: Colorectal (Bowel) Cancer
Department of Public Health and Clinical Medicine, Unit of Clinical Research Centre - Östersund, Umeå University , Sweden.


Huang J, Magnusson M, Törner A, et al.
Risk of pancreatic cancer among individuals with hepatitis C or hepatitis B virus infection: a nationwide study in Sweden.
Br J Cancer. 2013; 109(11):2917-23 [PubMed] Article available free on PMC after 26/11/2014 Related Publications
BACKGROUND: A few studies indicated that hepatitis C and hepatitis B virus (HCV/HBV) might be associated with pancreatic cancer risk. The aim of this nationwide cohort study was to examine this possible association.
METHODS: Hepatitis C virus- and hepatitis B virus-infected individuals were identified from the national surveillance database from 1990 to 2006, and followed to the end of 2008. The pancreatic cancer risk in the study population was compared with the general population by calculation of Standardized Incidence Ratios (SIRs), and with a matched reference population using a Cox proportional hazards regression model to calculate hazard ratios (HRs).
RESULTS: In total 340 819 person-years in the HCV cohort and 102 295 in the HBV cohort were accumulated, with 34 and 5 pancreatic cancers identified, respectively. The SIRHCV was 2.1 (95% confidence interval, CI: 1.4, 2.9) and the SIRHBV was 1.4 (0.5, 3.3). In the Cox model analysis, the HR for HCV infection was 1.9 (95% CI: 1.3, 2.7), diminishing to 1.6 (1.04, 2.4) after adjustment for potential confounders.
CONCLUSION: Our results indicated that HCV infection might be associated with an increased risk of pancreatic cancer but further studies are needed to verify such association. The results in the HBV cohort indicated an excess risk, however, without statistical significance due to lack of power.

Related: Cancer of the Pancreas Pancreatic Cancer
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 171 77 Stockholm, Sweden.


Liu C, Wang C, Wang K, et al.
SMYD3 as an oncogenic driver in prostate cancer by stimulation of androgen receptor transcription.
J Natl Cancer Inst. 2013; 105(22):1719-28 [PubMed] Related Publications
BACKGROUND: Androgen receptor (AR) is critical for prostate tumorigenesis and is frequently overexpressed during prostate cancer (PC) progression. However, few studies have addressed the epigenetic regulation of AR expression.
METHODS: We analyzed SMYD3 expression in human PC with Western blot and immunohistochemistry. SMYD3 expression was knocked down using short hairpin RNA (shRNA) or small interfering RNA (siRNA). Cell proliferation, colony formation, and apoptosis analyses and xenograft transplantation were performed to evaluate the impact of SMYD3 depletion on PC cells. AR expression and promoter activity were determined using real-time quantitative polymerase chain reaction, western blot, and luciferase reporter assay. AR promoter association with Sp1, SMYD3, and histone modifications was assessed by chromatin immunoprecipitation. Differences in AR mRNA abundance and promoter activity were analyzed using Wilcoxon signed-rank tests, SMYD3 expression was analyzed using with Mann-Whitney U tests for unpaired samples, and tumor weight was analyzed with Student t test. All statistical tests were two-sided.
RESULTS: The upregulation of SMYD3 protein expression was observed in seven of eight prostate tumor specimens, compared with matched normal tissues. Immunohistochemical analysis showed a strong SMYD3 staining in the nuclei of PC tissues in eight of 25 (32%) cases and in the cytoplasm in 23 out of 25 (92%) cases, whereas benign prostate tissue exhibited weak immunostaining. Depletion of SMYD3 by siRNA or shRNA inhibited PC cell proliferation (72 hours relative to 24 hours: control shRNA vs SMYD3 shRNA 1: mean fold change = 2.76 vs 1.68; difference = 1.08; 95% confidence interval = 0.78 to 1.38, P < .001), colony formation, cell migration, invasion, and xenograft tumor formation. Two functional SMYD3-binding motifs were identified in the AR promoter region.
CONCLUSIONS: SMYD3 promotes prostate tumorigenesis and mediates epigenetic upregulation of AR expression.

Related: AR: androgen receptor
Affiliations of authors: Department of Urology (CL, CW, KW, KY, JC, JL, HR, HL, ZX, YF), Department of General Surgery (LL, SH), and School of Nursing (LL), Shandong University Qilu Hospital, Jinan, Shandong, China; Central Research Laboratory of Shandong University Second Hospital, Jinan, Shandong...


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