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Cancer Statistics
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
Data from IARC GlobalCan (2012)
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

Backman S, Norlén O, Eriksson B, et al.
Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing.
Anticancer Res. 2017; 37(2):705-712 [PubMed] Related Publications
Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.
PATIENTS AND METHODS: Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.
RESULTS: Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.
CONCLUSION: Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.

Sivars L, Landin D, Grün N, et al.
Validation of Human Papillomavirus as a Favourable Prognostic Marker and Analysis of CD8(+) Tumour-infiltrating Lymphocytes and Other Biomarkers in Cancer of Unknown Primary in the Head and Neck Region.
Anticancer Res. 2017; 37(2):665-673 [PubMed] Related Publications
BACKGROUND: Human papillomavirus (HPV) is a favourable prognostic factor in oropharyngeal cancer. Moreover, we and others reported that HPV-positive cancer of unknown primary in the head and neck region (HNCUP) has better outcome than HPV-negative HNCUP. However, not all studies concord. Here, our previous finding was investigated in a new cohort and additional biomarkers were analyzed.
MATERIALS AND METHODS: A total of 19 HNCUPs diagnosed 2008-2013 were analyzed for HPV DNA by polymerase chain reaction assay (PCR) and p16 by immunohistochemistry (IHC). Thereafter, 69 HNCUPs diagnosed between 2000-2013 were analyzed for HPV16 mRNA by PCR (if HPV16DNA-positive) and cluster of differentiation 8 positive (CD8(+)) tumour-infiltrating lymphocytes (TILs) and human leukocyte antigen (HLA) class I-expression using IHC.
RESULTS: HPV DNA, alone and in combination with p16 overexpression, was validated as a favourable prognostic factor in HNCUP. HPV16 mRNA was present in most HPV16 DNA-positive cases, confirming HPV-driven carcinogenesis in HNCUP. High CD8(+) TIL counts indicated favourable prognosis.
CONCLUSION: HPV status is useful for the management of patients with HNCUP and the role of CD8(+) TILs should be further explored.

Andritsch E, Beishon M, Bielack S, et al.
ECCO Essential Requirements for Quality Cancer Care: Soft Tissue Sarcoma in Adults and Bone Sarcoma. A critical review.
Crit Rev Oncol Hematol. 2017; 110:94-105 [PubMed] Related Publications
BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Sarcoma: essential requirements for quality care • Sarcomas - which can be classified into soft tissue and bone sarcomas - are rare, but all rare cancers make up more than 20% of cancers in Europe, and there are substantial inequalities in access to high-quality care. Sarcomas, of which there are many subtypes, comprise a particularly complex and demanding challenge for healthcare systems and providers. This paper presents essential requirements for quality cancer care of soft tissue sarcomas in adults and bone sarcomas. • High-quality care must only be carried out in specialised sarcoma centres (including paediatric cancer centres) which have both a core multidisciplinary team and an extended team of allied professionals, and which are subject to quality and audit procedures. Access to such units is far from universal in all European countries. • It is essential that, to meet European aspirations for high-quality comprehensive cancer control, healthcare organisations implement the requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis and follow-up, to treatment, to improve survival and quality of life for patients.
CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality service for soft tissue sarcomas in adults and bone sarcomas. The ECCO expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary teams is guaranteed to all patients with sarcoma.

Beets G, Sebag-Montefiore D, Andritsch E, et al.
ECCO Essential Requirements for Quality Cancer Care: Colorectal Cancer. A critical review.
Crit Rev Oncol Hematol. 2017; 110:81-93 [PubMed] Related Publications
BACKGROUND: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Colorectal cancer: essential requirements for quality care CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality CRC service. The ECCO expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with CRC.

Solinas C, Pusole G, Demurtas L, et al.
Tumor infiltrating lymphocytes in gastrointestinal tumors: Controversies and future clinical implications.
Crit Rev Oncol Hematol. 2017; 110:106-116 [PubMed] Related Publications
Chronic inflammation following infections, autoimmune diseases or exposure to environmental irritants plays a crucial role in tumor development and influences the host immune response to neoplastic cells. The presence of an anti-tumor immune infiltrate is often associated with better outcomes in gastro-intestinal primary cancers, particularly in those with high microsatellite instability (MSI-H). Immunotherapeutic drugs inhibiting the PD-1 and PD-L1 pathway showed promising results in the treatment of these patients in the metastatic setting. The aim of this review is to resume the role tumor infiltrating lymphocytes (TILs) play in gastrointestinal tumors, underlining their potential value as a prognostic and predictive biomarker. TILs assessment could identify subsets of patients with high extent of TILs and better prognosis, that could be spared from adjuvant systemic treatments. Immune infiltration parameters might be additional predictors of a greater benefit from the immunotherapy with the immune checkpoint blockade.

Matikas A, Mistriotis D, Georgoulias V, Kotsakis A
Targeting KRAS mutated non-small cell lung cancer: A history of failures and a future of hope for a diverse entity.
Crit Rev Oncol Hematol. 2017; 110:1-12 [PubMed] Related Publications
Lung cancer remains the leading cause of cancer-related deaths in both men and women. However, the discovery of several oncogenic driver mutations and the development of immune checkpoint inhibitors resulted in improved clinical outcomes for most patients. Although activating KRAS mutations are the most common recurring molecular events in lung adenocarcinoma, little progress has been made during the past decades with no new agents being approved for this indication. The elucidation of the underlying biology of this diverse patient subgroup offers great potential and renewed hope regarding the rational development, rigorous evaluation and subsequent approval of novel targeted agents and combinations which will effectively suppress compensatory escape routes and the emergence of resistance, issues that have plagued previous attempts. Here, we review in a structured manner all aspects of KRAS positive non-small cell lung cancer, including the molecular biology, clinicopathologic characteristics, the prognostic and predictive value of KRAS mutations, as well as previous and contemporary approaches towards the treatment of this elusive target.

Mínguez P, Flux G, Genollá J, et al.
Whole-remnant and maximum-voxel SPECT/CT dosimetry in (131) I-NaI treatments of differentiated thyroid cancer.
Med Phys. 2016; 43(10):5279-5287 [PubMed] Related Publications
PURPOSE: To investigate the possible differences between SPECT/CT based whole-remnant and maximum-voxel dosimetry in patients receiving radio-iodine ablation treatment of differentiated thyroid cancer (DTC).
METHODS: Eighteen DTC patients were administered 1.11 GBq of (131) I-NaI after near-total thyroidectomy and rhTSH stimulation. Two patients had two remnants, so in total dosimetry was performed for 20 sites. Three SPECT/CT scans were performed for each patient at 1, 2, and 3-7 days after administration. The activity, the remnant mass, and the maximum-voxel activity were determined from these images and from a recovery-coefficient curve derived from experimental phantom measurements. The cumulated activity was estimated using trapezoidal-exponential integration. Finally, the absorbed dose was calculated using S-values for unit-density spheres in whole-remnant dosimetry and S-values for voxels in maximum-voxel dosimetry.
RESULTS: The mean absorbed dose obtained from whole-remnant dosimetry was 40 Gy (range 2-176 Gy) and from maximum-voxel dosimetry 34 Gy (range 2-145 Gy). For any given patient, the activity concentrations for each of the three time-points were approximately the same for the two methods. The effective half-lives varied (R = 0.865), mainly due to discrepancies in estimation of the longer effective half-lives. On average, absorbed doses obtained from whole-remnant dosimetry were 1.2 ± 0.2 (1 SD) higher than for maximum-voxel dosimetry, mainly due to differences in theS-values. The method-related differences were however small in comparison to the wide range of absorbed doses obtained in patients.
CONCLUSIONS: Simple and consistent procedures for SPECT/CT based whole-volume and maximum-voxel dosimetry have been described, both based on experimentally determined recovery coefficients. Generally the results from the two approaches are consistent, although there is a small, systematic difference in the absorbed dose due to differences in the S-values, and some variability due to differences in the estimated effective half-lives, especially when the effective half-life is long. Irrespective of the method used, the patient absorbed doses obtained span over two orders of magnitude.

Rollvén E, Abraham-Nordling M, Holm T, Blomqvist L
Assessment and diagnostic accuracy of lymph node status to predict stage III colon cancer using computed tomography.
Cancer Imaging. 2017; 17(1):3 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: To study different imaging criteria for prediction of lymph node metastases (Stage III disease) in colon cancer using CT.
METHODS: In a retrospective setting, 483 consecutive patients with histology proven colon cancer underwent elective primary resection during 2008-2011, a cohort of 119 patients were included. Contrast enhanced CT examinations, in portal-venous phase, were reviewed with assessment of the number of lymph nodes, their anatomical distribution, size, size ratio, internal heterogeneity, presence of irregular outer border and attenuation values. Sensitivity, specificity, PPV and NPV for each studied criteria for prediction of stage III disease was calculated.
RESULTS: According to histopathology 80 patients were stage I-II and 39 were stage III. Of the studied CT-criteria for lymph node metastases per patient, internal heterogeneity in at least one lymph node resulted in the best performance with sensitivity, specificity, PPV and NPV of 79, 84, 70 and 89%, Odds ratio (OR) 20. Presence of irregular outer border resulted in a sensitivity, specificity, PPV and NPV of 59, 81, 61 and 82%, OR 6.2. If both internal heterogeneity and/or irregular outer border was used as a criterion this resulted in a sensitivity, specificity, PPV and NPV of 85, 75, 62 and 91%, OR 16.5. None of the size criteria used were predictive for stage III disease.
CONCLUSIONS: When performing preoperative CT in patients with colon cancer, the imaging criteria that allow best prediction of stage III disease on CT are either presence of at least one lymph node with internal heterogeneity or internal heterogeneity and/or irregular outer border. These criteria have to be validated in a prospective study.

Sparber-Sauer M, Seitz G, Kirsch S, et al.
The impact of local control in the treatment of type II/III pleuropulmonary blastoma. Experience of the Cooperative Weichteilsarkom Studiengruppe (CWS).
J Surg Oncol. 2017; 115(2):164-172 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: This study aims at examining the potential survival benefits of primary versus secondary surgery in the management of children diagnosed with pleuropulmonary blastoma (PPB) type II/III.
PATIENTS AND METHODS: Disease characteristics, treatment, and survival of 29 children with localized PPB type II/III, treated in six prospective Cooperative Weichteilsarkom Studiengruppe (CWS) trials, were reviewed retrospectively.
RESULTS: Five year event free survival (EFS) and overall survival (OS) of children treated according to CWS protocols was 72%. Patients with tumors ≤10 cm had a 5 year OS of 91% versus 57% in patients with tumors >10 cm (P = 0.025). Five year OS of patients with macroscopically incomplete upfront resections was 44% as opposed to 68% in patients with delayed/secondary microscopically or macroscopically complete resection after an initial biopsy (P = 0.476). Ten patients died of disease, one patient died of second malignancy. Tumor size and complete tumor resection at any time were significant prognostic factors (P = 0.025/0.003) for EFS. EFS for microscopically complete, microscopically incomplete, and macroscopically incomplete resection at any time was 91%, 90%, and 25%, respectively (P = 0.01).
CONCLUSIONS: Primary or secondary microscopically/macroscopically complete tumor resections in combination with chemotherapy correlates with long term survival in children with PPB. J. Surg. Oncol. 2017;115:164-172. © 2017 Wiley Periodicals, Inc.

Strosberg J, El-Haddad G, Wolin E, et al.
Phase 3 Trial of (177)Lu-Dotatate for Midgut Neuroendocrine Tumors.
N Engl J Med. 2017; 376(2):125-135 [PubMed] Related Publications
Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ((177)Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either (177)Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) ((177)Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the (177)Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the (177)Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the (177)Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the (177)Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Conclusions Treatment with (177)Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the (177)Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).

Prabhakar N, Zhang J, Desai D, et al.
Stimuli-responsive hybrid nanocarriers developed by controllable integration of hyperbranched PEI with mesoporous silica nanoparticles for sustained intracellular siRNA delivery.
Int J Nanomedicine. 2016; 11:6591-6608 [PubMed] Free Access to Full Article Related Publications
Small interfering RNA (siRNA) is a highly potent drug in gene-based therapy with the challenge being to deliver it in a sustained manner. The combination of mesoporous silica nanoparticles (MSNs) and polycations in the confined pore space allows for incorporation and controlled release of therapeutic siRNA payloads. We hereby constructed MSNs with expanded mesopores and pore-surface-hyperbranched poly(ethyleneimine) (PEI) tethered with redox-cleavable linkers that could carry a high payload of siRNA (120 mg·g(-1)). The developed nanocarriers were efficiently taken up by cancer cells and were subsequently able to escape to the cytoplasm from the endosomes, most likely owing to the integrated PEI. Triggered by the intracellular redox conditions, the siRNA was sustainably released inside the cells over a period of several days. Functionality of siRNAs was demonstrated by using cell-killing siRNA as cargo. Despite not being the aim of the developed system, in vitro experiments using cell-killing siRNAs showed that the efficacy of siRNA transfection was comparable to the commercial in vitro transfection agent Lipofectamine. Consequently, the developed MSN-based delivery system offers a potential approach to hybrid nanocarriers for more efficient and long-term siRNA delivery and, in a longer perspective, in vivo gene silencing for RNA interference (RNAi) therapy.

Baghbani E, Baradaran B, Pak F, et al.
Suppression of protein tyrosine phosphatase PTPN22 gene induces apoptosis in T-cell leukemia cell line (Jurkat) through the AKT and ERK pathways.
Biomed Pharmacother. 2017; 86:41-47 [PubMed] Related Publications
The aim of this study was to investigate the effect of specific PTPN22 small interfering RNAs (siRNAs) on the viability and induction of apoptosis in Jurkat cells and to evaluate apoptosis signaling pathways. In this study, Jurkat cells were transfected with specific PTPN22 siRNA. Relative PTPN22 mRNA expression was measured by Quantitative Real-time PCR. Western blotting was performed to determine the protein levels of PTPN22, AKT, P-AKT, ERK, and P-ERK. The cytotoxic effects of PTPN22 siRNA were determined using the MTT assay. Apoptosis was quantified using TUNEL assay and flow cytometry. Results showed that in Jurkat cells after transfection with PTPN22 siRNA, the expression of PTPN22 in both mRNA and protein levels was effectively reduced. Moreover, siRNA transfection induced apoptosis on the viability of T-cell acute leukemia cells. More importantly, PTPN22 positively regulated the anti-apoptotic AKT kinase, which provides a powerful survival signal to T-ALL cells as well as the suppression of PTPN22 down regulated ERK activity. Our results suggest that the PTPN22 specific siRNA effectively decreases the viability of T-cell acute leukemia cells, induces apoptosis in this cell line, and therefore could be considered as a potent adjuvant in T-ALL therapy.

Arenaz Búa B, Olsson R, Westin U, Rydell R
The Pharyngoesophageal Segment After Total Laryngectomy.
Ann Otol Rhinol Laryngol. 2017; 126(2):138-145 [PubMed] Related Publications
OBJECTIVE: The aim of the present study was to characterize the pharyngoesophageal segment in laryngectomees who rated themselves as functional tracheoesophageal speakers.
METHODS: Voice perceptual assessment, high-resolution videomanometry of swallowing and phonation, and high-speed camera recording during phonation provided information about the anatomy and function of the pharyngoesophageal segment.
RESULTS: Fourteen patients were included in the study. The voice assessments presented high intra/inter-listener reliability. We found a significant correlation between roughness and poor voice quality, hyperfunction and poor intelligibility, and poor voice quality, long time since the operation, and old age. High-resolution videomanometry during phonation revealed decreasing mean pressures from the distal esophagus to the pharynx and confirmed low resting pressures at the pharyngoesophageal segment and low esophageal peristaltic contraction pressures after laryngectomy in comparison to normal subjects. The neoglottis shape was mainly circular and presented a strong mucosal wave in most of the patients on the high-speed camera recording.
CONCLUSIONS: Perceptual voice assessment and high-speed camera recordings provided baseline information about voice characteristics and vibration regularity of the neoglottis. Additionally, the quantitative measures obtained with high-resolution videomanometry may have clinical applicability as reference data in voice rehabilitation after total laryngectomy.

Thellenberg-Karlsson C, Nyman C, Nilsson S, et al.
Bone-targeted Novel Cytotoxic Polybisphosphonate Conjugate in Castration-resistant Prostate Cancer: A Multicenter Phase 1 Study.
Anticancer Res. 2016; 36(12):6499-6504 [PubMed] Related Publications
BACKGROUND: Osteodex (ODX) is a cytotoxic bone-targeting polybisphosphonate, intended for treatment of bone metastasis from castration-resistant prostate cancer (CRPC). The primary objective of this study was to describe the tolerability and toxicity of such treatment by defining its maximum tolerated dose (MTD) and dose-limiting toxicity (DLT).
PATIENTS AND METHODS: Twenty-eight patients with castration-resistant prostate cancer and confirmed bone metastasis were assigned to seven infusions of ODX every third week, divided in seven ascending dose cohorts.
RESULTS: No DLT's were observed and as pre-specified, the highest dose administered was defined as MTD. In total, 206 adverse events (AE) were recorded and 13,6% were classified as treatment-related, while none were serious or severe (SAE). No cumulative toxicity and no renal toxicity were recorded.
CONCLUSION: ODX was well tolerated, with few and mild side-effects and with apparent treatment efficacy in the highest dose cohort. Further clinical development is currently in progress.

Strandberg S, Karlsson CT, Ogren M, et al.
11C-Acetate-PET/CT Compared to 99mTc-HDP Bone Scintigraphy in Primary Staging of High-risk Prostate Cancer.
Anticancer Res. 2016; 36(12):6475-6479 [PubMed] Related Publications
AIM: The aim of this study was to evaluate the detection rate of bone metastases and the added value of (11)C-acetate (ACE) positron-emission tomography/computed tomography (PET/CT) compared to bone scintigraphy (BS) in high-risk prostate cancer (PC).
MATERIALS AND METHODS: A total of 66 untreated patients with high-risk PC with ACE-PET/CT and planar BS findings within 3 months of each other were retrospectively enrolled. Findings were compared and verified with follow-up data after an average of 26 months.
RESULTS: The rate of detection of bone metastases was superior with ACE-PET/CT compared to BS (p<0.01). Agreement between the methods and between BS and follow-up was moderate (Cohen's kappa coefficient of 0.64 and 0.66, respectively). Agreement between ACE-PET/CT and follow-up was excellent (kappa coefficient of 0.95). Therapy was changed in 11% of patients due to ACE-PET/CT results.
CONCLUSION: ACE-PET/CT performed better than planar BS in detection of bone metastases in high-risk PC. ACE-PET/CT findings influenced clinical management.

Johnsson A, Broberg P, Johnsson A, et al.
Occupational sedentariness and breast cancer risk.
Acta Oncol. 2017; 56(1):75-80 [PubMed] Related Publications
BACKGROUND: Epidemiological studies have indicated that physical activity reduces the risk of developing breast cancer. More recently, sedentary behavior has been suggested as a risk factor independent of physical activity level. The purpose of the present study was to investigate occupational sedentariness and breast cancer risk in pre- and postmenopausal women.
MATERIALS AND METHODS: In a population-based prospective cohort study (n = 29 524), working history was assessed by a questionnaire between 1990 and 1992. Participants were classified as having: (1) sedentary occupations only; (2) mixed occupations or (3) non-sedentary occupations only. The association between occupational sedentariness and breast cancer incidence was analyzed by Cox regression, adjusted for known risk factors and participation in competitive sports.
RESULTS: Women with a working history of occupational sedentariness had a significantly increased risk of breast cancer (adjusted HR 1.20; 95% CI 1.05, 1.37) compared with those with mixed or non-sedentary occupations. The association was stronger among women younger than 55 years (adjusted HR 1.54; 95% CI 1.20, 1.96), whereas no association was seen in women 55 years or older. Adjustment for participation in competitive sports did not change the association.
CONCLUSIONS: We found that occupational sedentariness was associated with increased breast cancer risk, especially in women younger than 55 years. This may be a modifiable risk factor by planning breaks during the working day. Whether this reduces the risk of breast cancer needs to be further studied.

Cheson BD, Trask PC, Gribben JG, et al.
Health-related quality of life and symptoms in patients with rituximab-refractory indolent non-Hodgkin lymphoma treated in the phase III GADOLIN study with obinutuzumab plus bendamustine versus bendamustine alone.
Ann Hematol. 2017; 96(2):253-259 [PubMed] Free Access to Full Article Related Publications
We present health-related quality of life (HRQoL) data from GADOLIN, comparing bendamustine (B) alone or combined with obinutuzumab (G-B) in rituximab-refractory indolent non-Hodgkin lymphoma patients. The Functional Assessment of Cancer Treatment-Lymphoma (FACT-Lym) questionnaire was administered on day 1 of cycles 1, 3, and 5 during treatment, at end of induction (EOI), bi-monthly for 2 years during maintenance/follow-up, and annually during extended follow-up until progression/death. Time to first ≥6-point worsening from baseline in the FACT-Lym trial outcome index (TOI) was estimated. Minimally important differences at individual subscale and total score level were used to define the proportion of patients reporting improvement on the FACT-Lym lymphoma-specific subscale (≥3 points), FACT-Lym TOI (≥6 points), and FACT-Lym total score (≥7 points). Overall, 396 patients were randomized. Analysis was conducted when 175 Independent Review Committee-assessed progression-free survival (PFS) events were observed. Questionnaire completion rates were generally balanced between arms at baseline, EOI, and final follow-up. Median time to ≥6-point worsening from baseline on the FACT-Lym TOI was 8.0 months in the G-B arm and 4.6 months in the B arm (HR 0.74; 95% CI 0.56-0.98). More G-B patients reported meaningful improvements on the FACT-Lym questionnaire subscales. Results were similar when follicular lymphoma patients were analyzed separately. The delayed time to worsening and greater proportion of patients reporting meaningful improvement in HRQoL in the G-B arm suggest that benefit in PFS is not at the expense of an increase in treatment-related toxicity that could lead to reduced HRQoL.

Hjälm-Eriksson M, Ullén A, Johansson H, et al.
Comorbidity as a predictor of overall survival in prostate cancer patients treated with external beam radiotherapy combined with HDR brachytherapy boosts.
Acta Oncol. 2017; 56(1):21-26 [PubMed] Related Publications
BACKGROUND: The risk stratification currently applied prior to curative treatment for localized prostate cancer (PC) does not take into account comorbidity or age. Therefore, we investigated the impact of comorbidity on overall survival (OS) in PC patients treated with external beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy boost.
MATERIAL AND METHODS: At a single center, 611 consecutive patients diagnosed with localized PC from 1998 to 2004 underwent definitive EBRT (50 Gy) and HDR brachytherapy boosts (2 × 10 Gy) combined with neoadjuvant total androgen blockade. Comorbidity was assessed with the Charlson comorbidity score. The impact of risk factors on OS and disease-free survival (DFS) was calculated using Cox proportional hazard ratios. Risk groups were defined as follows: low-risk PC: PSA <10, WHO grade 1 and T stage 1; high-risk PC: PSA >20 and/or WHO grade 3 and/or T stage 3a; intermediate-risk PC representing patients who did not fit either the low- or high-risk PC group.
RESULTS: Mean age in the study cohort was 66.4 years, and 51% of the patients reported some degree of comorbidity. Divided into risk groups 8.2% were categorized as low-risk, 64% as intermediate-risk and 27.8% as high-risk PC. Overall 10-year survival was 72.2%, and 89% of the patients were relapse-free. In the univariate and multivariate analyses using Cox proportional hazard ratios, age, comorbidity and T stage were statistically significant predictors of OS: hazard ratios 1.56, 1.44 and 1.2 (p-values .002, .04 and .05), respectively. WHO grade, PSA at diagnosis, T stage and comorbidity were also significant predictors of DFS (p-values .0001, .0001, .009 and .003, respectively).
CONCLUSION: Comorbidity assessed with the Charlson score predicts OS in patients with localized PC treated with curative intent using combined EBRT and HDR brachytherapy boost, and should be considered when making decisions before radical treatment.

Plato N, Martinsen JI, Sparén P, et al.
Occupation and mesothelioma in Sweden: updated incidence in men and women in the 27 years after the asbestos ban.
Epidemiol Health. 2016; 38:e2016039 [PubMed] Free Access to Full Article Related Publications
OBJECTIVES: We updated the Swedish component of the Nordic Occupational Cancer (NOCCA) Study through 2009 in order to investigate the incidence of mesothelioma of the peritoneum and pleura in both genders, and explored occupational exposures that may be associated with mesothelioma.
METHODS: The Swedish component of the NOCCA Study includes 6.78 million individuals. Data from this cohort were linked to the population-based Swedish Cancer Registry and Swedish Total Population Registry for three periods between 1961 and 2009, and then further linked to the Swedish NOCCA job-exposure matrix, which includes 25 carcinogenic substances and the corresponding exposure levels for 280 occupations. Multivariate analysis was used to calculate standardized incidence ratios (SIRs) for mesothelioma of the peritoneum and pleura by gender, occupational category, carcinogenic substance, and for multiple occupational exposures simultaneously.
RESULTS: A total of 3,716 incident mesotheliomas were recorded (21.1% in women). We found a significantly increased risk of mesothelioma in 24 occupations, as well as clear differences between the genders. Among men, increased risks of mesothelioma of the pleura were observed in male-dominated occupations, with the greatest elevation of risk among plumbers (SIR, 4.99; 95% confidence interval, 4.20 to 5.90). Among women, increased risks were observed in sewing workers, canning workers, packers, cleaners, and postal workers. In multivariate analysis controlling for multiple occupational exposures, significant associations were only observed between asbestos exposure and mesothelioma.
CONCLUSIONS: Asbestos exposure was associated with mesothelioma incidence in our study. The asbestos ban of 1982 has yet to show any clear effect on the occurrence of mesothelioma in this cohort. Among women, the occupations of canning workers and cleaners showed increased risks of mesothelioma of the pleura without evidence of asbestos exposure.

Hovén E, Grönqvist H, Pöder U, et al.
Impact of a child's cancer disease on parents' everyday life: a longitudinal study from Sweden.
Acta Oncol. 2017; 56(1):93-100 [PubMed] Related Publications
BACKGROUND: A child's cancer disease may disrupt the daily life of the affected family for a long period. The aim was to describe restrictions on parents' leisure activities and work/studies during and after the child's treatment.
METHODS: This study used data from a cohort of mothers and fathers (n = 246) of children diagnosed with cancer. Data was collected five times from two months after diagnosis to one year after end of treatment. Reports of restrictions were evaluated over time, between mothers and fathers, and in relation to parent-reported child symptom burden (The Memorial Symptom Assessment Scale) and partial post-traumatic stress disorder (PTSD) (The PTSD Checklist-Civilian Version).
RESULTS: Two (51%) and four (45%) months after diagnosis, about half reported that their leisure activities were restricted at least some of the time. Corresponding percentages for restrictions on work/studies were 84% and 77%. One year after end of treatment, the great majority reported that their leisure activities (91%) and/or work/studies (76%) were never/seldom restricted. During treatment, more mothers than fathers reported restrictions on work/studies all/most of the time. After end of treatment, gender was only related to reports of restrictions among parents not reporting partial PTSD. More parents who reported being restricted all/most of the time also reported partial PTSD and/or a greater symptom burden for the child.
CONCLUSION: Parents report frequent restrictions on everyday life during treatment. One year after end of treatment, parents report only a limited impact of the child's cancer on their leisure activities and work/studies. More parents who report restrictions also report partial PTSD and/or a greater child symptom burden. The effect of gender on restrictions varies depending on reports of partial PTSD. Future studies of gender differences regarding the impact of a child's cancer on parents' everyday life should thus consider mothers' and fathers' level of psychological distress.

Foukakis T, von Minckwitz G, Bengtsson NO, et al.
Effect of Tailored Dose-Dense Chemotherapy vs Standard 3-Weekly Adjuvant Chemotherapy on Recurrence-Free Survival Among Women With High-Risk Early Breast Cancer: A Randomized Clinical Trial.
JAMA. 2016; 316(18):1888-1896 [PubMed] Related Publications
Importance: Standard dosing of chemotherapy based on body surface area results in marked interpatient variation in pharmacokinetics, toxic effects, and efficacy. Whether tailored dosing can improve outcomes is unknown, as is the role of dose-dense adjuvant chemotherapy.
Objective: To determine whether tailored dose-dense adjuvant chemotherapy improves the outcomes of early breast cancer compared with a standard 3-weekly chemotherapy schedule.
Design, Setting, and Participants: A randomized, open-label, phase 3 trial of women aged 65 years and younger who had surgery for nonmetastatic node-positive or high-risk node-negative breast cancer at 86 sites in Sweden, Germany, and Austria between February 20, 2007, and September 14, 2011.
Interventions: Patients were randomized 1:1 either to 4 cycles of leukocyte nadir-based tailored and dose-dense adjuvant epirubicin and cyclophosphamide every 2 weeks followed by 4 cycles of tailored dose-dense docetaxel every 2 weeks, or to standard-interval chemotherapy with 3 cycles of fluorouracil and epirubicin-cyclophosphamide every 3 weeks followed by 3 cycles of docetaxel every 3 weeks.
Main Outcomes and Measures: The primary end point was breast cancer recurrence-free survival (BCRFS). Secondary end points included 5-year event-free survival (EFS), distant disease-free survival (DDFS), overall survival (OS), and rates of grade 3 or 4 toxic effects.
Results: Among 2017 randomized patients (1006 in the tailored dose-dense group and 1011 in the control group; median [IQR] age, 51 [45-58] years; 80% with hormone receptor-positive tumors; 97% with node-positive disease), 2000 received study treatment (≥1 cycle of chemotherapy; 1001 in the tailored dose-dense group and 999 in the control group). After a median follow-up of 5.3 years (IQR, 4.5-6.1 years), 269 BCRFS events were reported, 118 in the tailored dose-dense group and 151 in the control group (HR, 0.79; 95% CI, 0.61-1.01; log-rank P = .06; 5-year BCRFS, 88.7% vs 85.0%). The tailored dose-dense group had significantly better EFS than the control group (HR, 0.79; 95% CI, 0.63-0.99; P = .04; 5-year EFS, 86.7% vs 82.1%). The groups did not differ in OS (HR, 0.77; 95% CI, 0.57-1.05; P = .09; 5-year OS, 92.1% vs 90.2%) or DDFS (HR, 0.83; 95% CI, 0.64-1.08; P = .17; 5-year DDFS, 89.4% vs 86.7%). Grade 3 or 4 nonhematologic toxic effects occurred in 527 (52.6%) in the tailored dose-dense group and 366 (36.6%) in the control group.
Conclusions and Relevance: Among women with high-risk early breast cancer, the use of tailored dose-dense chemotherapy compared with standard adjuvant chemotherapy did not result in a statistically significant improvement in breast cancer recurrence-free survival. Nonhematologic toxic effects were more frequent in the tailored dose-dense group.
Trial Registration: clinicaltrials.gov Identifier: NCT00798070; isrctn.org Identifier: ISRCTN39017665.

Lindqvist EK, Landgren O, Lund SH, et al.
History of autoimmune disease is associated with impaired survival in multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study.
Ann Hematol. 2017; 96(2):261-269 [PubMed] Free Access to Full Article Related Publications
Multiple myeloma (MM) is a plasma cell disorder preceded by monoclonal gammopathy of undetermined significance (MGUS). Incidence of MM and MGUS is higher among patients with autoimmune disease. The aim of this study was to determine whether a history of autoimmunity has an impact on survival in MM and MGUS. Using high-quality national Swedish registries, we identified 8367 patients with MM, 18,768 patients with MGUS, and 110,251 matched control subjects, and obtained information on previous autoimmune disease in patients and controls. Cox regression was used to calculate hazard ratios (HRs) for overall survival with 95 % confidence intervals (CIs). In patients with MM and a prior autoimmune disease, the risk of death was significantly increased, HR = 1.2 (95 % CI 1.2-1.3) compared to MM patients with no history of autoimmunity. In MGUS patients, a prior autoimmune disease was associated with a significantly 1.4-fold elevated risk of death (95 % CI 1.3-1.4). When analyzing different types of autoimmune diseases, a history of ulcerative colitis had a stronger impact on survival in MM than in controls. Our findings that a history of autoimmune disease has a negative impact on survival in MM and MGUS could be due to shared underlying common genetic factors, or that patients with a history of autoimmunity develop more severe cases of MM and MGUS, or cumulative comorbidity in the individual. Our results suggest that more attention should be paid to comorbidity as a prognostic factor in MGUS and MM, and underlines the need for studies aimed at tailoring therapy according to comorbidity.

Nahálková J
The protein-interaction network with functional roles in tumorigenesis, neurodegeneration, and aging.
Mol Cell Biochem. 2016; 423(1-2):187-196 [PubMed] Related Publications
The present review summarizes the knowledge about a protein-interaction network, which includes proteins with significant functions in the mechanisms of aging and age-related diseases. All the detected interacting proteins TPPII, p53, MYBBP1A, CDK2 and SIRT7, SIRT6, and CD147 are suitable for the development of antitumor therapeutics and treatments for diseases of aging. TPPII and SIRT6 directly affect glucose metabolism which drive malignant growth. In addition, SIRT6 activators are attractive candidates for Alzheimer's disease (AD) due to the protection effect of SIRT6 overexpression from DNA damage. TPPII activity exhibits a decreasing effect on mTOR signaling, and its requirement for the degradation of Aβ peptides in the human fibroblasts suggests that it has dual functions in tumorigenesis and AD-related pathology. Likewise, the direct promotion of the invasiveness of breast epithelial cells and the contribution to the Aβ degradation by stimulating the matrix metalloproteinases production suggest a double functional role for CD147. An association of the partial portion of cellular CD147 to γ-secretase further supports the functional relation to AD pathology. The animal and cellular models with downregulated or knockout TPPII, p53, SIRT6, SIRT7, and MYBBP1A expression levels illustrate similar functions of the interacting proteins. They demonstrate similar effects on the length of life span, premature aging, and lipid metabolism. The presented protein-interaction network is relevant to the discoveries of the mechanisms of tumorigenesis, aging, and neurodegeneration.

Koyi H, Hillerdal G, Kölbeck KG, et al.
Non-small Cell Lung Cancer (NSCLC) in Octogenarians in Clinical Practice.
Anticancer Res. 2016; 36(10):5397-5402 [PubMed] Related Publications
BACKGROUND/AIM: Globally, an increasing proportion of cancer patients are aged >65 years and many are aged >70 years. Treatment of the elderly with lung cancer has, therefore, become an important issue. We performed a retrospective study of our patients to demonstrate how octogenarians with non-small cell lung cancer (NSCLC) are treated in real-life clinical practice.
PATIENTS AND METHODS: This was a retrospective observational study of all elderly (≥80 years) patients with NSCLC referred to the Department of Respiratory Medicine and Allergy, Karolinska Hospital, Sweden, 2003-2010, and followed until June, 2016.
RESULTS: In total, 452 patients, 216 (47.8%) men and 236 (52.2%) women, were included. The mean and median age was 83 years; 28 (6.2%) were aged 90 years or more. Current or former smokers constituted 91.1%, with men having smoked more (p<0.001). There was no difference in performance status (PS) between genders with PS 0-1 in 45.4%, PS 2 in 25.6% and PS3-4 in 29%. About a third each was diagnosed in stages 1-II, III and IV. Adenocarcinoma was most common (45.6%), 18.1% had squamous cell carcinoma, while histological diagnosis was unavailable in 23.2%. Best supportive care (BSC) was given only to 209 patients (46.2%). Potentially curative therapy was administered to 16.5% of men and 20.3% of the women with surgery performed in 35 patients (7.8%) and stereotactic body radiation therapy (SBRT) in 48 patients (10.6%). Chemotherapy was given to 51 patients (11.2%) and palliative radiotherapy to 77 (17.0%). Second-line chemotherapy was given in 4% and third-line in 1.5%. Only one patient received fourth-line. Male patients who received chemotherapy survived a mean of 281 days and for female patients it was 332 days (not significant). Median overall survival (OS) was 115 days in patients receiving BSC and 362 days in patients given any therapy. Patients who underwent surgery for stage I-II had a median OS of 5.6 years compared to 3.5 years for patients given SBRT.
CONCLUSION: Treatment of NSCLC patients 80 years and older with any modality is feasible with a good PS. Survival is fairly good with surgery or SBRT.

Rubio CA, Schmidt PT
Gut-associated Lymphoid Tissue (GALT) Carcinoma or Dome Carcinoma?
Anticancer Res. 2016; 36(10):5385-5387 [PubMed] Related Publications
BACKGROUND/AIM: The vast majority of colorectal carcinomas (CRCs) evolve from mucosa not associated to lymphoid tissues aggregates via the adenoma-carcinoma sequence or via the serrated pathway. Rarely CRCs evolve from gut mucosa associated to lymphoid tissue (GALT).
MATERIALS AND METHODS: Based on the presence of a circumscribed elevation in the colorectal mucosa, GALT carcinomas are also referred to as dome carcinomas (DC). Descriptions of the surface mucosa covering 21 GALT-CRCs appearing in pathological reports were reviewed.
RESULTS: Three of the 21 GALT-CRCs fulfilled the criteria of dome carcinoma. Of the remaining 18 GALT-CRCs, nine were described as polypoid lesions, five as plaque-like lesions, two as sessile elevated lesions or mass, one as ulcerated and one as histological finding. Hence, only 14.3% (n=3) of the 21 GALT-CRCs displayed a dome configuration, whereas the majority, 85.7% (n=18), exhibited structures other than dome shapes at gross or at histologic examination.
CONCLUSION: It becomes apparent that by using "dome" in addressing carcinomas in the colorectal mucosa, many cases of GALT carcinomas might be overlooked. Another drawback of using the "dome" nomenclature is that dome-like outlines may be detected in small metastatic tumors in the submucosa or in small colorectal carcinomas not arising from GALT mucosa. Instead, by using "GALT carcinoma", that is the histologic diagnosis in addressing these neoplasias, all cases of GALT-CRCs will be included.

Køstner AH, Kersten C, Löwenmark T, et al.
The prognostic role of systemic inflammation in patients undergoing resection of colorectal liver metastases: C-reactive protein (CRP) is a strong negative prognostic biomarker.
J Surg Oncol. 2016; 114(7):895-899 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Systemic inflammation has been associated with poor survival in several tumor types, but has been less extensively studied in resectable metastatic disease. The aim of the present study was to evaluate the prognostic role of CRP in colorectal cancer patients with liver metastases (CRLM) compared to conventional tumor- and patient-related clinicopathological features as well as other indicators of the systemic inflammatory response (SIR).
METHODS: A multinational retrospective study of 492 CRLM patients undergoing potentially curative resection of liver metastases between 1999 and 2009. Clinicopathological findings and the SIR markers CRP, hypoalbuminemia, and their combined Glasgow Prognostic Score (GPS) were analyzed.
RESULTS: Multivariate analysis showed that preoperative CRP >10 mg/L was a strong predictor of compromised survival (HR = 1.72, 95%CI 1.84-2.50, P < 0.01). Patients with CRP ≤10 mg/L had a median survival of 4.27 years compared to only 47 days in patients with CRP ≥30 mg/L (P < 0.01). Similarly, increased GPS was independently predictive of poor survival (HR 1.67, 95%CI 1.22-2.27, P < 0.01), but hypoalbuminemia alone did not have significant prognostic value.
CONCLUSIONS: CRP alone is a strong prognostic factor, following curative resection of colorectal liver metastases and should be taken into consideration when selecting treatment strategies in CRLM patients. J. Surg. Oncol. 2016;114:895-899. © 2016 2016 Wiley Periodicals, Inc.

Thomsen FB, Folkvaljon Y, Brasso K, et al.
Prognostic implications of 2005 Gleason grade modification. Population-based study of biochemical recurrence following radical prostatectomy.
J Surg Oncol. 2016; 114(6):664-670 [PubMed] Related Publications
OBJECTIVE: To assess the impact of the 2005 modification of the Gleason classification on risk of biochemical recurrence (BCR) after radical prostatectomy (RP).
PATIENTS AND METHODS: In the Prostate Cancer data Base Sweden (PCBaSe), 2,574 men assessed with the original Gleason classification and 1,890 men assessed with the modified Gleason classification, diagnosed between 2003 and 2007, underwent primary RP. Histopathology was reported according to the Gleason Grading Groups (GGG): GGG1 = Gleason score (GS) 6, GGG2 = GS 7(3 + 4), GGG3 = GS 7(4 + 3), GGG4 = GS 8 and GGG5 = GS 9-10. Cumulative incidence and multivariable Cox proportional hazards regression models were used to assess difference in BCR.
RESULTS: The cumulative incidence of BCR was lower using the modified compared to the original classification: GGG2 (16% vs. 23%), GGG3 (21% vs. 35%) and GGG4 (18% vs. 34%), respectively. Risk of BCR was lower for modified versus original classification, GGG2 Hazard ratio (HR) 0.66, (95%CI 0.49-0.88), GGG3 HR 0.57 (95%CI 0.38-0.88) and GGG4 HR 0.53 (95%CI 0.29-0.94).
CONCLUSION: Due to grade migration following the 2005 Gleason modification, outcome after RP are more favourable. Consequently, outcomes from historical studies cannot directly be applied to a contemporary setting. J. Surg. Oncol. 2016;114:664-670. © 2016 Wiley Periodicals, Inc.

Bubendorf L, Büttner R, Al-Dayel F, et al.
Testing for ROS1 in non-small cell lung cancer: a review with recommendations.
Virchows Arch. 2016; 469(5):489-503 [PubMed] Free Access to Full Article Related Publications
Rearrangements of the ROS1 gene occur in 1-2 % of non-small cell lung cancers (NSCLCs). Crizotinib, a highly effective inhibitor of ROS1 kinase activity, is now FDA-approved for the treatment of patients with advanced ROS1-positive NSCLC. Consequently, focus on ROS1 testing is growing. Most laboratories currently rely on fluorescence in situ hybridisation (FISH) assays using a dual-colour break-apart probe to detect ROS1 rearrangements. Given the rarity of these rearrangements in NSCLC, detection of elevated ROS1 protein levels by immunohistochemistry may provide cost-effective screening prior to confirmatory FISH testing. Non-in situ testing approaches also hold potential as stand-alone methods or complementary tests, including multiplex real-time PCR assays and next-generation sequencing (NGS) platforms which include commercial test kits covering a range of fusion genes. In order to ensure high-quality biomarker testing, appropriate tissue handling, adequate control materials and participation in external quality assessment programmes are essential, irrespective of the testing technique employed. ROS1 testing is often only considered after negative tests for EGFR mutation and ALK gene rearrangement, based on the assumption that these oncogenic driver events tend to be exclusive. However, as the use of ROS1 inhibitors becomes routine, accurate and timely detection of ROS1 gene rearrangements will be critical for the optimal treatment of patients with NSCLC. As NGS techniques are introduced into routine diagnostic practice, ROS1 fusion gene testing will be provided as part of the initial testing package.

Khan AS, Hojjat-Farsangi M, Daneshmanesh AH, et al.
Dishevelled proteins are significantly upregulated in chronic lymphocytic leukaemia.
Tumour Biol. 2016; 37(9):11947-11957 [PubMed] Related Publications
Dishevelled (DVL) proteins are components of the Wnt signalling pathways, and increased expression is associated with various malignancies. Information on DVLs in chronic lymphatic leukaemia (CLL) is limited. The aim of the present study was to investigate the role of DVLs in CLL cells and association with Wnt pathways downstream of ROR1. DVL1, 2 and 3 were exclusively expressed in CLL cells as compared to normal peripheral blood mononuclear cells (PBMCs). The expression of DVL1 and DVL3 proteins was significantly more pronounced in progressive than in non-progressive disease (p < 0.01), whereas the level of DVL2 was significantly higher in non-progressive as compared to progressive disease (p < 0.001). Treatment of CLL cells with anti-ROR1 specific monoclonal antibodies induced dephosphorylation of ROR1 as well as of tyrosine and serine residues of both DVL2 and DVL3. However, gene silencing of DVLs in the CLL cell line (EHEB) did not induce detectable apoptosis. Non-progressive CLL patients had a different protein activity pattern with regard to Wnt signalling pathway proteins as GSK-3β, β-catenin and AKT as compared to progressive disease. The DVL2 protein may play a role in the activation of signalling pathways in CLL during early stages of the disease, while DVL1 and 3 may have a role in later phases of the leukaemia.

Kumar JK, Aronsson AC, Pilko G, et al.
A clinical evaluation of the TK 210 ELISA in sera from breast cancer patients demonstrates high sensitivity and specificity in all stages of disease.
Tumour Biol. 2016; 37(9):11937-11945 [PubMed] Free Access to Full Article Related Publications
Thymidine kinase (TK1) is an enzyme involved in DNA synthesis that leaks into the blood as a result of high cell turnover, particularly in the case of cancer. Serum TK1 activity has been used for prognosis and monitoring of leukemia and lymphoma patients for many years. Here, we describe the first clinical results with the newly developed TK 210 ELISA from AroCell AB. Sera from 124 breast cancer patients with known TNM classification along with sera from 53 healthy females were analyzed by TK 210 ELISA for TK1 protein and TK1 activity levels by the (3)[H]-deoxythymidine (dThd) phosphorylation assay. The limit of detection for the TK 210 ELISA was 0.17 ng/ml, and 60 % of the sera from female blood donors were below this value. The median TK1 levels found in sera from breast cancer patients with T1 to T4 stage disease were 0.31, 0.46, 0.47, and 0.55 ng/ml, and these levels significantly differed from healthy controls. The median values of the biomarker CA 15-3 were also increased in patient sera from T1 to T4 patients (16, 34, 36, 40 U/ml, respectively). TK 210 ELISA showed significantly higher sensitivity for the T1 and T2 breast cancer patients compared to the TK activity assay. The combination of the TK1 ELISA and CA 15-3 biomarkers demonstrated a significant increase in sensitivity up to 15 % compared to each marker alone. This evaluation of the TK 210 ELISA strongly suggests that it can provide independent and complementary information for patients with breast cancer.

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