| 12261. |
- Borg, Sixten, et al.
(författare)
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Performance of standardized cancer patient pathways in Sweden visualized using observational data and a state-transition model
- 2023
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Ingår i: Scientific Reports. - 2045-2322. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Standardized Cancer Patient Pathways (CPPs) were introduced in Swedish healthcare starting in 2015 to improve diagnostics for patients with symptoms of cancer, patient satisfaction and equity of care between healthcare providers. An inclusion target and a time target were set. Our primary aim was to visualize the patient population going through CPPs, in terms of investigation time and indications of the various outcomes including cancer diagnoses. Our secondary aims were to examine if targets were met, and to examine frequencies of undetected cancer. We collected data from 19,204 patients starting in a CPP, and 7895 patients diagnosed with cancer in 2018 in a region of Sweden. A state transition model was developed and used as analytical framework, and patients were mapped over time in the states of the model. Visualization of the patient-flow through the model illustrates speed of investigation, time to treatment, frequencies of detected and undetected cancer. Twelve CPPs out of 28 met the inclusion target, five met the time target. After suspicion of cancer rejected, 0.8% of patients were diagnosed with the primarily suspected cancer, 1.0% with another cancer. In patients not meeting the criteria for well-founded suspicion less than 3% were later diagnosed with cancer. The visualization of the patient flow into and through standardized cancer patient pathways illustrates investigation time, events occurring and outcomes. The use of standardized cancer patient pathways detects cancer efficiently.
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| 12262. |
- Borg, Sixten, et al.
(författare)
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The cost-effectiveness of treatment with erythropoietin compared to red blood cell transfusions for patients with chemotherapy induced anaemia: a Markov model.
- 2008
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 47:6, s. 1009-1017
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anaemia is a common complication of chemotherapy. As anaemia can lead to e.g. fatigue, depression, social isolation and chest pain it diminishes physical capacity and quality of life. It is generally accepted that symptomatic anaemia should be corrected. Treatment options include red blood cell transfusion (RBCT), erythropoietin (EPO) administration or a combination of both. OBJECTIVE: The objective of this study was to carry out a cost-effectiveness analysis of treatment with EPO (epoetin alfa), compared to treatment with RBCT for patients with chemotherapy-induced anaemia in Sweden from a health care perspective. METHOD: A model was developed for estimating incremental costs and QALY gains associated with EPO treatment compared to treatment with RBCTs, based on a model commissioned by the UK National Institute for Health and Clinical Excellence and adjusted to reflect Swedish treatment practice. Data regarding patient characteristics, response rates, and RBCT was derived from a Swedish observational study of EPO treatment in cancer patients with chemotherapy related anaemia. Swedish guidelines and unit costs were used throughout the study. A systematic review of EPO for treatment of anaemia associated with cancer was used to estimate QALY gains associated with changes in Hb-concentrations in our model. RESULTS: The model's results validate well to real world data from three major hospitals in Sweden. The cost per QALY gained from administration of EPO was estimated at EUR 24,700 in the base case analysis. Practicing an EPO treatment target Hb-level of 12 g/dl yields a cost per QALY about 40% lower than practicing a Hb-target level of 13 g/dl, which is in agreement with updated recommendations of using a 12 g/dl target. CONCLUSION: The estimated cost per QALY falls well within the range acceptable in Sweden when practicing a Hb-target level of 12 g/dl. The incremental cost of elevating Hb-levels above 13 g/dl is very high in relation to the incremental QALY gain achieved.
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| 12263. |
- Borg, Åke, et al.
(författare)
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c-myc amplification is an independent prognostic factor in postmenopausal breast cancer
- 1992
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 51:5, s. 687-691
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Tidskriftsartikel (refereegranskat)abstract
- The c-myc proto-oncogene was analyzed in 311 cases of primary breast cancer, in 8% of which it was found to be amplified, usually at moderately increased copy number (2-5 copies). The adjacent pvt gene was co-amplified with c-myc in all tumors analyzed. C-myc amplification was significantly correlated to a high S-phase fraction and to amplification of the c-erbB-2 proto-oncogene. Weak relationships were found between c-myc amplification and the presence of lymph-node metastasis, advanced stage, DNA non-diploidy and premenopausal status, but not tumor size, estrogen receptor or progesterone receptor status, or int-2 amplification. C-myc amplification, and especially a high gene copy number (greater than 5 copies), was significantly related to early recurrence and death in breast cancer, a relationship seen in both the lymph-node-negative and node-positive subcategories. A particularly strong correlation with poor clinical outcome was seen in postmenopausal patients (p greater than 0.0005), an association which persisted in multivariate survival analysis. We conclude that the activation of c-myc is indeed associated with rapidly growing and progressive breast cancer. Gene amplification, on the other hand, is relatively infrequent and occurs mostly at low copy number, implying that tumors are heterogeneous with respect to cell clones harboring c-myc amplification. An immunohistochemical assessment would more accurately illustrate the importance of c-myc activation in human breast cancer. However, the obvious instability of the c-myc transcript and translate suggests that c-myc is not a suitable prognostic marker for routine purposes.
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| 12264. |
- Borg, Åke, et al.
(författare)
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Chromosome I alterations in breast cancer : Allelic loss on Ip and Iq Is related to lymphogenic metastases and poor prognosis
- 1992
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Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 5:4, s. 311-320
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Tidskriftsartikel (refereegranskat)abstract
- The development of human breast cancer is characterized by a variety of genetic alterations, and cytogenetic analyses have documented the consistent involvement of both arms of chromosome I. In the present study, molecular markers detecting restriction fragment length polymorphisms were used in pairwise screening of normal and tumor DNA to determine the frequency of allelic imbalance in breast tumors. Loss of heterozygosity (LOH) in the polymorphic epithelial mucin (PEM or MUCI) gene at 1q21 was found in 16% of 89 informative (constitutionally heterozygous) cases, whereas gain in intensity of one allelic band was more frequent (37%), a total of 47% of cases manifesting either allelic loss or gain. Three additional tumors manifested a structural alteration. Allelic loss or gain in the PEM gene was not associated with other prognostic factors, e.g., tumor size, lymph node status, steroid receptors, DNA ploidy, S phase fraction, protooncogene amplification, histological type, or patient age. However, LOH in the PEM gene was significantly correlated with early disease recurrence (P = 0.006). LOH on 1p was found in 27% of 117 informative cases, using probes for either DIS57 or DIZ2 located at 1p33‐p35 and 1p36, respectively. Somatic allelic imbalance on 1p and 1q seemed to be independent events and not the effect of loss of a whole chromosome 1. LOH on 1 p was significantly correlated to the presence of lymph node metastasis, to larger tumor size, and to DNA nondiploidy, but no correlation was found to disease outcome at this limited duration of follow‐up (median 29 months). ©1992 Wiley‐Liss, Inc.
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| 12265. |
- Borg, Åke, et al.
(författare)
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ERBB2 amplification in breast cancer with a high rate of proliferation
- 1991
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Ingår i: Oncogene. - 1476-5594. ; 6:1, s. 137-143
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Tidskriftsartikel (refereegranskat)abstract
- The ERBB2 proto-oncogene was studied in 539 invasive primary breast tumors and was found amplified (2- greater than 30 copies) in 19%. Amplification was correlated to most known risk factors, including; large tumor size, lymph node positivity and many tumor involved nodes, advanced stage, low patient age (less than 40 years), non-diploidy and hypertetraploidy, and most significantly (P less than 0.00001) to the absence of steroid receptors and to a high rate of proliferation (flow cytometric determined S phase fraction). ERBB2 amplification was strongly associated (P less than 0.0001) with early recurrence and death in breast cancer among node-positive patients. This connection did not, however, remain in multivariate analyses. No correlations to clinical outcome were seen among node-negative patients. Similarly, non-diploid, but not diploid, amplified tumors were particularly aggressive. Furthermore, ERBB2 amplification was associated with a high rate of proliferation and poor prognosis in steroid receptor positive, but not receptor negative tumors. In progesterone receptor positive breast cancer, amplification was an independent and with node status equally powerful (P less than 0.0001) predictor of poor survival. It is concluded that ERBB2 activity is related to an increased tumor growth rate but not directly to metastasizing ability. Its clinical relevance as a prognostic factor may be in selecting a high risk subgroup of breast cancer, in general considered as being of good prognosis.
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| 12266. |
- Borg, Åke
(författare)
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Hereditary prostate cancer: a new piece of the puzzle.
- 2001
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 7:2, s. 153-155
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Tidskriftsartikel (refereegranskat)abstract
- An eagerly awaited prostate cancer susceptibility gene has been announced. But does the candidate live up to expectations?
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| 12267. |
- Borg, Åke, et al.
(författare)
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High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families
- 2000
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Ingår i: Journal of the National Cancer Institute. - 0027-8874. ; 92:15, s. 6-1260
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: : Inherited mutations in the CDKN2A tumor suppressor gene, which encodes the p16(INK4a) protein, and in the cyclin-dependent kinase 4 (CDK4) gene confer susceptibility to cutaneous malignant melanoma. We analyzed families with two or more cases of melanoma for germline mutations in CDKN2A and CDK4 to elucidate the contribution of these gene defects to familial malignant melanoma and to the occurrence of other cancer types.METHODS: : The entire CDKN2A coding region and exon 2 of the CDK4 gene of an affected member of each of 52 families from southern Sweden with at least two cases of melanoma in first- or second-degree relatives were screened for mutations by use of polymerase chain reaction-single-strand conformation polymorphism analysis. Statistical tests were two-sided.RESULTS: : CDKN2A mutations were found in 10 (19%) of the 52 families. Nine families carried an identical alteration consisting of the insertion of arginine at position 113 of p16(INK4a), and one carried a missense mutation, in which the valine at position 115 was replaced with a glycine. The 113insArg mutant p16(INK4a) was unable to bind cdk4 and cdk6 in an in vitro binding assay. Six of the 113insArg families had at least one member with multiple primary melanomas; the 113insArg families also had a high frequency of other malignancies-in particular, breast cancer (a total of eight cases compared with the expected 2.1; P =.0014) and pancreatic cancer (a total of six cases compared with the expected 0.16; P<.0001). Families with breast cancer also had a propensity for multiple melanomas in females, suggesting that a sex-dependent factor may modify the phenotypic expression of CDKN2A alterations.CONCLUSIONS: : Our findings confirm that the majority of CDKN2A-associated melanoma families in Sweden are due to a single founder mutation. They also show that families with the CDKN2A 113insArg mutation have an increased risk not only of multiple melanomas and pancreatic carcinoma but also of breast cancer.
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| 12268. |
- Borg, Åke, et al.
(författare)
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Novel germline p16 mutation in familial malignant melanoma in southern Sweden
- 1996
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Ingår i: Cancer Research. - 0008-5472. ; 56:11, s. 500-2497
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Tidskriftsartikel (refereegranskat)abstract
- The p16 (CDKN2/MTS1/INK4a) malignant melanoma susceptibility gene was analyzed in 10 melanoma kindreds from southern Sweden using single-stranded conformation polymorphism analysis of all three exons and flanking intron regions followed by sequence analysis. A novel germline mutation, constituting an in-frame 3-bp duplication at nucleotide 332 in exon 2, was identified in two families (Lund M2 and M9). The mutation results in an insertion of Arg at codon 105, which interrupts the last of the four ankyrin repeats of the p16 protein, motifs which have been demonstrated as important in binding and inhibiting the activity of cyclin D-dependent kinases 4 and 6 in cell cycle G1 phase regulation. All five tested individuals of Lund M2 and M9 affected by melanoma were mutation carriers, as were five melanoma-free individuals. Other malignancies observed in gene carriers or obligate carriers included cervical, breast, and pancreatic carcinomas and a non-Hodgkin's lymphoma. Analysis of microsatellite markers adjacent to the p16 gene at chromosomal region 9p21 revealed that both families share a common haplotype, in keeping with a common ancestor.
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| 12269. |
- Borg, Åke, et al.
(författare)
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Predicting the future of breast cancer.
- 2003
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Ingår i: Nature Medicine. - : Springer Science and Business Media LLC. - 1546-170X .- 1078-8956. ; 9:1, s. 16-18
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Tidskriftsartikel (refereegranskat)
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| 12270. |
- Borgatti, Antonella, et al.
(författare)
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Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR.
- 2017
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Ingår i: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 16:5, s. 956-965
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Tidskriftsartikel (refereegranskat)abstract
- Sarcomas differ from carcinomas in their mesenchymal origin. Therapeutic advancements have come slowly so alternative drugs and models are urgently needed. These studies report a new drug for sarcomas that simultaneously targets both tumor and tumor neovasculature. eBAT is a bispecific angiotoxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epidermal growth factor (EGF) and the amino terminal fragment (ATF) of urokinase. Here, we study the drug in an in vivo "ontarget" companion dog trial since eBAT effectively kills canine hemangiosarcoma (HSA) and human sarcoma cells in vitro. We reasoned the model has value due to the common occurrence of spontaneous sarcomas in dogs and a limited lifespan allowing for rapid accrual and data collection. Splenectomized dogs with minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin in an adaptive dose-finding, phase I-II study of 23 dogs with spontaneous, stage I-II, splenic HSA. eBAT improved 6-month survival from <40% in a comparison population to ~70% in dogs treated at a biologically active dose (50 µg/kg). Six dogs were long-term survivors, living >450 days. eBAT abated expected toxicity associated with EGFR-targeting, a finding supported by mouse studies. Urokinase plasminogen activator receptor (uPAR) and EGFR are targets for human sarcomas, so thorough evaluation is crucial for validation of the dog model. Thus, we validated these markers for human sarcoma targeting in the study of 212 human and 97 canine sarcoma samples. Our results support further translation of eBAT for human patients with sarcomas and perhaps other EGFR-expressing malignancies.
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