| 1. |
- Adra, Jamila, et al.
(författare)
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Blood biomarkers for neuroaxonal injury and astrocytic activation in chemotherapy-induced peripheral neuropathy
- 2024
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Ingår i: ACTA ONCOLOGICA. - 0284-186X .- 1651-226X. ; 63, s. 636-641
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome side effect in patients exposed to taxanes in the treatment of cancer and may affect quality of life dramatically. Here we assessed whether serum levels of neurofilament light (NfL) and tau (two neuroaxonal injury biomarkers) and glial fibrillary acidic protein (GFAP, a biomarker for astrocytic activation) correlate with the development of CIPN in the adjuvant setting of early breast cancer. Materials and methods: Using ultrasensitive single molecule array technology, serum levels of NfL, GFAP, and tau were measured before and every 3 weeks in 10 women receiving adjuvant EC (epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2) every 3 weeks x 3, followed by weekly paclitaxel 80 mg/ m2 x 9-12 weeks after surgery due to early breast cancer. CIPN was graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0) and the questionnaire EORTC QLQ CIPN-20. Results: Serum levels of GFAP increased successively during cycles of EC. NfL increased instead in response to the treatment of paclitaxel. NfL and GFAP continued to rise throughout exposure of cumulatively higher doses of paclitaxel and were reduced 3 months after the end of chemotherapy. Serums levels of tau were marginally affected by exposure to chemotherapy. Women with worse symptoms of CIPN had higher concentrations of NfL than women with mild symptoms of CIPN. Interpretation: NfL and GFAP are promising biomarkers to identify women at risk of developing CIPN. Larger prospective studies are now needed.
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| 2. |
- Fohlin, Helena, et al.
(författare)
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Breast cancer hormone receptor levels and benefit from adjuvant tamoxifen in a randomized trial with long-term follow-up
- 2024
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Ingår i: ACTA ONCOLOGICA. - : Medical Journal Sweden AB. - 0284-186X .- 1651-226X. ; 63, s. 535-541
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hormone receptor positivity predicts benefit from endocrine therapy but the knowledge about the long-term survival of patients with different tumor receptor levels is limited. In this study, we describe the 25 years outcome of tamoxifen (TAM) treated patients. Patients and methods: Between 1983 and 1992, a total of 4,610 postmenopausal patients with early-stage breast cancer were randomized to receive totally 2 or 5 years of TAM therapy. After 2 years, 4,124 were alive and free of breast cancer recurrence. Among these, 2,481 had demonstrated estrogen receptor positive (ER+) disease. From 1988, the Abbot enzyme immunoassay became available and provided quantitative receptor levels for 1,210 patients, for which our analyses were done. Results: After 5 years of follow-up, when all TAM treatment was finished, until 15 years of follow-up, breast cancer mortality for patients with ER+ disease was significantly reduced in the 5-year group as compared with the 2-year group (hazard ratios [HR] 0.67, 95% confidence intervals [CI] 0.55-0.83, p < 0.001). After 15 years, the difference between the groups remained but did not increase further. A substantial benefit from prolonged TAM therapy was only observed for the subgroup of patients with ER levels below the median (HR = 0.62, 95% CI 0.46-0.84, p = 0.002). Similarly, patients with progesterone receptor negative (PR-) disease did benefit from prolonged TAM treatment. For patients with progesterone receptor positive (PR+) disease, there was no statistically significant benefit from more than 2 years of TAM. Interpretation: As compared with 2 years of adjuvant TAM, 5 years significantly prolonged breast cancer-specific survival. The benefit from prolonged TAM therapy was statistically significant for patients with ER levels below median or PR-negative disease. There was no evident benefit from prolonged TAM for patients with high ER levels or with PR+ tumors.
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| 3. |
- Heyman, Sofia, et al.
(författare)
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Reduction of elective lymph node volume in radiotherapy of early anal squamous cell cancer : a comparative study between two Swedish university hospitals
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63:1, s. 118-124
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Tidskriftsartikel (refereegranskat)abstract
- Background: Anal squamous cell cancer (ASCC) in early stages (T1–2N0M0) is treated with chemoradiotherapy with a 3-year overall survival (OS) exceeding 90%. In Swedish guidelines, it has been optional to include the external iliac and presacral lymph node (LN) stations in radiotherapy (RT) treatment fields in early ASCC. Two Swedish hospitals treating ASCC (SU: Sahlgrenska University Hospital; UU: Uppsala University Hospital) have chosen different approaches since 2010.Material and methods: This study included consecutive patients with early ASCC (T1–2N0M0) treated between 2010 and 2017 at both sites (SU n = 70; UU n = 46). Data were retrieved from medical records and RT charts.Results: At SU, the external iliac and presacral LN stations were included in elective LN irradiation in 96.8% (n = 60) and 95.2% (n = 59) patients compared to 2.4% (n = 1) and 29.3% (n = 12) at UU. The mean elective LN volume was 2,313 cc (interquartile range [IQR] 1,951–2,627) in the SU cohort compared to 1,317 cc (IQR 1,192–1,528) in the UU cohort, p < 0.0001. No case of regional LN recurrence was seen in either cohort. Disease specific survival (DSS) at 5 years was 95.7% (confidence interval [CI] 90.1–100.0) in the SU cohort and 97.8% (CI 93.2–100.0) in the UU cohort (p 0.55). OS at 5 years was 84.5% (CI 76.1–93.0) in the SU cohort and 82.6% (CI 69.6–89.1) in the UU cohort (p 0.8).Interpretation: We found no differences in regional recurrence, DSS or OS between the cohorts treated with different elective LN volumes. In this population-based study, reduction of RT volume in early ASCC did not lead to inferior outcome.
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| 4. |
- Karlsson, Anna, et al.
(författare)
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The effect of tinzaparin on biomarkers in FIGO stages III-IV ovarian cancer patients undergoing neoadjuvant chemotherapy - the TABANETOC trial: study protocol for a randomized clinical multicenter trial
- 2024
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Ingår i: ACTA ONCOLOGICA. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 580-585
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tinzaparin, a low-molecular weight heparin (LMWH), has shown anti-neoplastic properties in animal models and in in vitro studies of human cancer cell lines. The reduction of CA-125 levels during neoadjuvant chemotherapy (NACT) in patients with epithelial ovarian cancer (EOC) co-varies with the prognosis; the larger the decrease in CA-125, the better the prognosis. Purpose: This study aims to evaluate the potential anti-neoplastic effects of tinzaparin by investigating changes in serum CA-125 levels in advanced EOC patients who receive NACT. Material and methods: This is an open randomized multicenter pilot trial. Forty patients with EOC selected to receive NACT will be randomized 1:1 to receive daily addition of tinzaparin or no tinzaparin. The processing and treatment of the patients will otherwise follow the recommendations in the Swedish National Guidelines for Ovarian Cancer. Before every cycle of chemotherapy, preoperatively, and 3 weeks after the last cycle of chemotherapy, a panel of biomarkers, including CA-125, will be measured. Patients: Inclusion criteria are women aged 18 years or older, World Health Organization performance status 0-1, histologically confirmed high-grade serous, endometrioid or clear cell EOC, International Federation of Gynecology and Obstetrics (FIGO) stages III-IV. In addition, a CA-125 level of >= 250 kIE/L at diagnosis. Exclusion criteria are contraindications to LMWH, ongoing or recent treatment with unfractionated heparin, LMWH, warfarin or non-vitamin K antagonist oral anticoagulants. Interpretation: This study will make an important contribution to the knowledge of the anti-neoplastic effects of tinzaparin in EOC patients and may thus guide the planning of a future study on the impact of tinzaparin on survival in EOC.
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| 5. |
- Perman, Mats, 1969, et al.
(författare)
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Doses to the right coronary artery and the left anterior descending coronary artery and death from ischemic heart disease after breast cancer radiotherapy: a case-control study in a population-based cohort.
- 2024
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 63, s. 240-247
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Tidskriftsartikel (refereegranskat)abstract
- Doses to the coronary arteries in breast cancer (BC) radiotherapy (RT) have been suggested to be a risk predictor of long-term cardiac toxicity after BC treatment. We investigated the dose-risk relationships between near maximum doses (Dmax) to the right coronary artery (RCA) and left anterior descending coronary artery (LAD) and ischemic heart disease (IHD) mortality after BC RT.In a cohort of 2,813 women diagnosed with BC between 1958 and 1992 with a follow-up of at least 10 years, we identified 134 cases of death due to IHD 10-19 years after BC diagnosis. For each case, one control was selected within the cohort matched for age at diagnosis. 3D-volume and 3D-dose reconstructions were obtained from individual RT charts. We estimated the Dmax to the RCA and the LAD and the mean heart dose (MHD). We performed conditional logistic regression analysis comparing piecewise spline transformation and simple linear modeling for best fit.There was a linear dose-risk relationship for both the Dmax to the RCA (odds ratio [OR]/Gray [Gy] 1.03 [1.01-1.05]) and the LAD (OR/Gy 1.04 [1.02-1.06]) in a multivariable model. For MHD there was a linear dose-risk relationship (1,14 OR/Gy [1.08-1.19]. For all relationships, simple linear modelling was superior to spline transformations.Doses to both the RCA and LAD are independent risk predictors of long-term cardiotoxicity after RT for BC In addition to the LAD, the RCA should be regarded as an organ at risk in RT planning.
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| 6. |
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| 7. |
- Albertsson, Per, 1964, et al.
(författare)
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Dose effects of continuous vinblastine chemotherapy on mammalian angiogenesis mediated by VEGF-A.
- 2008
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:2, s. 293-300
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Tidskriftsartikel (refereegranskat)abstract
- Low-dose continuous or metronomic chemotherapy with several agents can exert significant antiangiogenic effects, as shown in preclinical studies. Therapy of this kind is generally well tolerated compared with conventional chemotherapy with high, temporally spaced out bolus doses. A critical point emerges when the effects on angiogenesis of low-toxic metronomic doses of chemotherapeutics in preclinical studies are to be transferred to clinical protocols, as there is a risk that a virtually non-toxic dose might also be ineffective; clearly, dose-effect data are important. We therefore sought to investigate whether a dose-dependent response exists in metronomic vinblastine chemotherapy. The surrogate tumor-free rat mesentery model, allowing the study of antiangiogenic effects per se, was used. Following systemically administered metronomic chemotherapy, it closely reflects the indirectly assessed antiangiogenic and growth-retarding effects in a syngenic cancer model. VEGF-A, which is a central proangiogenic factor in most tumors, was administered i.p. to induce angiogenesis in the mesenteric test tissue and, using morphometry, the angiogenesis-modulating effects of vinblastine were assessed in terms of objective quantitative variables. We report that continuous vinblastine treatment with an apparently non-toxic dose (1.0 mg/kg/week or 0.143 mg/kg/day) for 10 days, and a dose that substantially inhibited the physiologic body-weight gain (2.0 mg/kg/week or 0.286 mg/kg/day) for 6 days, demonstrates a dose-response relationship; the high dose significantly suppresses angiogenesis. To our knowledge, no previous study has reported on a dose-dependent antiangiogenic effect by continuous or metronomic vinblastine treatment in a mammalian in vivo model.
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| 8. |
- Albertsson, Per, 1964, et al.
(författare)
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Low-dose continuous 5-fluorouracil infusion stimulates VEGF-A-mediated angiogenesis.
- 2009
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 48:3, s. 418-25
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Tumor growth is angiogenesis-dependent. Animal studies have demonstrated that frequent administration of chemotherapeutics may have marked antiangiogenic effects and improved antitumor effects, with less severe toxic side-effects than intermittent maximum tolerated dose chemotherapy. Currently, research focused on low-dose antiangiogenic chemotherapy is increasing. We have recently reported that certain chemotherapeutics, including 5-fluorouracil (5-FU), may in fact stimulate angiogenesis in the tumor-free rat mesenteric window assay. The aim of the present study was to extend the investigation of the angiogenesis-modulating effects of 5-FU by prolonging the continuous infusion treatment time. METHOD: Angiogenesis was induced in the mesenteric test tissue in adult male Sprague-Dawley rats by i.p. injection of VEGF-A, which is a key angiogenic factor in most tumors. During the subsequent angiogenesis, 5-FU was delivered continuously for 14 days by an osmotic pump implanted subcutaneously. The angiogenic response was analyzed by morphometry in the mesenteric windows. RESULTS: The 14-days continuous infusion of 5-FU significantly stimulated angiogenesis. Thus the possibility that the previously reported surprising proangiogenic effect of 5-FU reflected an insufficiently long treatment period can be ruled out. CONCLUSION: The finding that continuously infused 5-FU is able to stimulate angiogenesis in the present rat model of angiogenesis warrants investigation of the mechanisms behind this unexpected finding. It may further have implications for the choice of antiangiogenic chemotherapeutic schedule used for cancer patients.
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| 9. |
- Albertsson, Per, 1964, et al.
(författare)
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On metronomic chemotherapy: modulation of angiogenesis mediated by VEGE-A
- 2006
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 45:2, s. 144-55
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Tidskriftsartikel (refereegranskat)abstract
- Tumors are angiogenesis dependent. Preclinical studies have shown that well-tolerated continuous low dose, i.e. metronomic, chemotherapy can exert significant antiangiogenic effects per se and thereby a greater antitumor influence than conventional chemotherapy with high, spaced-out bolus doses. There are however, no means of quantitatively assessing the antiangiogenic effect of chemotherapy in tumors. We therefore used a surrogate tumor-free, non-surgical rat mesentery model and quantitatively studied the dose effect of metronomic treatment with cisplatin, cyclophosphamide, doxorubicin, fluorouracil and paclitaxel on VEGF-A-mediated angiogenesis, a characteristic of tumors. Cyclophosphamide and paclitaxel treatment exerted significant dose-dependent antiangiogenic effects, whereas doxorubicin treatment produced insignificant effects. By contrast, metronomic cisplatin and fluorouracil treatment occasionally significantly stimulated angiogenesis in a dose-dependent, non-linear manner. To our knowledge, this is the first report of metronomic chemotherapy stimulating angiogenesis in vivo. The data suggest that the angiogenic response to cisplatin, cyclophosphamide, fluorouracil and paclitaxel was significantly influenced by the presence of antioxidants in the vehicles or when co-treated with N-acetylcystein, a widely used free-radical scavenger. The data relating to the metronomic scheduling were compared with bolus treatment data for the identical agent formulations in the same experimental model. Cisplatin, cyclophosphamide and paclitaxel caused approximately the same overall, agent-specific angiogenesis-modulating effects following metronomic and bolus treatments. Moreover, apparently secondary delayed effects of chemotherapy affected capillary sprouting.
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| 10. |
- Alevronta, Eleftheria, et al.
(författare)
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Dose-response relationships for an atomized symptom of fecal incontinence after gynecological radiotherapy.
- 2013
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Taylor & Francis. - 1651-226X .- 0284-186X. ; 52:4, s. 719-26
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. The aim of this study was to investigate what bowel organ and delivered dose levels are most relevant for the development of 'emptying of all stools into clothing without forewarning' so that the related dose-responses could be derived as an aid in avoiding this distressing symptom in the future. Material and methods. Of the 77 gynecological cancer survivors treated with radiotherapy (RT) for gynecological cancer, 13 developed the symptom. The survivors were treated between 1991 and 2003. The anal-sphincter region, the rectum, the sigmoid and the small intestines were all delineated and the dose-volume histograms were exported for each patient. The dose-volume parameters were estimated fitting the data to the Relative Seriality (RS), the Lyman and the generalized Equivalent Uniform Dose (gEUD) model. Results. The dose-response parameters for all three models and four organs at risk (OARs) were estimated. The data from the sigmoid fits the studied models best: D50 was 58.8 and 59.5 Gy (RS, Lyman), γ50 was 1.60 and 1.57 (RS, Lyman), s was 0.32, n was 0.13 and a was 7.7 (RS, Lyman, gEUD). The estimated volume parameters indicate that the investigated OARs behave serially for this endpoint. Our results for the three models studied indicate that they have the same predictive power (similar LL values) for the symptom as a function of the dose for all investigated OARs. Conclusions. In our study, the anal-sphincter region and sigmoid fit our data best, but all OARs were found to have steep dose-responses for 'emptying of all stools into clothing without forewarning' and thus, the outcome can be predicted with an NTCP model. In addition, the dose to the four studied OARs may be considered when minimizing the risk of the symptom.
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