| 1. |
- Brusselaers, Nele, et al.
(författare)
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Tumour staging of oesophageal cancer in the Swedish Cancer Registry : a nationwide validation study
- 2015
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Ingår i: Acta Oncologica. - Stockholm : Karolinska Institutet, Dept of Molecular Medicine and Surgery. - 1651-226X.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Tumour stage was introduced to the Swedish Cancer Registry in 2004, but this key variable for prognostic research has not yet been validated. We validated the tumour stage data in surgically treated oesophageal cancer patients. Material and Methods: Completeness and accuracy of tumour stage according to the TNM system (“Tumour Node Metastasis”) in the Cancer Registry were compared with a cohort study including comprehensive tumour stage data based on the pathological TNM of almost all patients operated for oesophageal cancer in 2006-2010 in Sweden. Results: Of the 397 patients with pathological TNM data in the comparison cohort, the Cancer Registry reported an overall TNM stage in 390 patients (98.2%), which was based on the pathological TNM of 104 patients (26.2%), the clinical TNM of 183 patients (46.1%), and the pathological or clinical TNM (undefined) of 110 patients (27.7%). The completeness for the separate T, N, and M components was 89.4%, 90.9%, and 85.1%, respectively. The concordance with tumour stage was 98.2%, while it was 51.1%, 70.5%, and 80.4% for the separate T, N, and M components, respectively. While the concordance with tumour stage was high for all TNM assessment groups (98.1-98.4%), the concordance of the T and N components was highest when using pathological TNM (82.7% and 95.2%, respectively), and the concordance of the M component was highest when using clinical TNM (88.5%). Conclusion: Although the overall completeness of tumour stage is high, the recording of pathological TNM stage and individual components could be improved within the Swedish Cancer Registry.
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| 2. |
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| 3. |
- Engström, Terese, et al.
(författare)
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Hormone receptor mRNA and protein levels as predictors of premenopausal tamoxifen benefit
- 2024
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Ingår i: Acta Oncologica. - : Medical Journal Sweden AB. - 0284-186X .- 1651-226X. ; 63, s. 125-136
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Tamoxifen remains an important adjuvant treatment in premenopausal patients with hormone receptor-positive breast cancer. Thus, determination of hormone receptors is important. Here, we compare cytosol-based methods, immunohistochemistry (IHC), and gene expression (GEX) analysis for determining hormone receptor status in premenopausal breast cancer patients from a randomised tamoxifen trial, to evaluate their performance in identifying patients that benefit from tamoxifen. Patients and Methods: Premenopausal patients (n=564) were randomised to 2 years of tamoxifen or no systemic treatment. Estrogen receptor (ER) and progesterone receptor (PR) status by protein expression measured by cytosol-based methods and IHC, and mRNA by GEX analysis were compared in 313 patients with available data from all methods. Kaplan Meier estimates and Cox regression were used to evaluate the treatment-predictive value for recurrence-free interval (RFi) and overall survival (OS). Median follow-up for event-free patients was 26 (RFi) and 33 (OS) years. Results: The mRNA data of ESR1 and PGR distributed bimodally, patterns confirmed in an independent cohort. Kappa-values between all methods were 0.76 and 0.79 for ER and PR, respectively. Tamoxifen improved RFi in patients with ER-positive (ER+) or PR-positive (PR+) tumours (Hazard Ratio [HR] and 95% confidence interval [CI]), cytosol-ER+ 0.53 [0.36–0.79]; IHC-ER+ 0.55 [0.38–0.79]; GEX-ER+ 0.54 [0.37–0.77]; cytosol-PR+ 0.49 [0.34–0.72]; IHC-PR+ 0.58 [0.40–0.85]; GEX-PR+ 0.55 [0.38–0.80]). Results were similar for OS. Interpretation: These methods can all identify patients that benefit from 2 years of tamoxifen with equal performance, indicating that GEX data might be used to guide adjuvant tamoxifen therapy.
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| 4. |
- Hörberger, Filip, et al.
(författare)
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Pencil beam scanning proton therapy for mediastinal lymphomas in deep inspiration breath-hold : a retrospective assessment of plan robustness
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 62-69
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Tidskriftsartikel (refereegranskat)abstract
- Purpose/background: The aim of this study was to evaluate pencil beam scanning (PBS) proton therapy (PT) in deep inspiration breath-hold (DIBH) for mediastinal lymphoma patients, by retrospectively evaluating plan robustness to the clinical target volume (CTV) and organs at risk (OARs) on repeated CT images acquired throughout treatment.Methods: Sixteen mediastinal lymphoma patients treated with PBS-PT in DIBH were included. Treatment plans (TPs) were robustly optimized on the CTV (7 mm/4.5%). Repeated verification CTs (vCT) were acquired during the treatment course, resulting in 52 images for the entire patient cohort. The CTV and OARs were transferred from the planning CT to the vCTs with deformable image registration and the TPs were recalculated on the vCTs. Target coverage and OAR doses at the vCTs were compared to the nominal plan. Deviation in lung volume was also calculated.Results: The TPs demonstrated high robust target coverage throughout treatment with D98%,CTV deviations within 2% for 14 patients and above the desired requirement of 95% for 49/52 vCTs. However, two patients did not achieve a robust dose to CTV due to poor DIBH reproducibility, with D98%,CTV at 78 and 93% respectively, and replanning was performed for one patient. Adequate OAR sparing was achieved for all patients. Total lung volume variation was below 10% for 39/52 vCTs.Conclusion: PBS PT in DIBH is generally a robust technique for treatment of mediastinal lymphomas. However, closely monitoring the DIBH-reproducibility during treatment is important to avoid underdosing CTV and achieve sufficient dose-sparing of the OARs.
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| 5. |
- Wagenius, Gunnar, et al.
(författare)
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First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden : A Population-based Real-world Study with Focus on Immunotherapy
- 2024
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 63, s. 198-205
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. MATERIALS AND METHODS: Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. RESULTS: A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. INTERPRETATION: The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.
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| 6. |
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| 7. |
- Ask, Samuel, et al.
(författare)
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The effect of psychosocial interventions for sexual health in patients with pelvic cancer : a systematic review and meta-analysis
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden AB. - 0284-186X .- 1651-226X. ; 63:1, s. 230-239
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Forskningsöversikt (refereegranskat)abstract
- Aim: The aim of this systematic review and meta-analysis was to explore and evaluate the effect of psychosocial interventions in improving sexual health outcomes among post-treatment patients with pelvic cancer.Methods: Inclusion and exclusion criteria were pelvic cancer survivors; psychosocial interventions; studies with a control group and measures of sexual health. Five databases were searched for literature along with an inspection of the included studies' reference lists to extend the search. Risk of bias was assessed with the RoB2 tool. Standardised mean difference (SMD) with a random effects model was used to determine the effect size of psychosocial interventions for sexual health in patients with pelvic cancers.Results: Thirteen studies were included, with a total number of 1,541 participants. There was a large heterogeneity regarding the type of psychosocial intervention used with the source found in a leave one out analysis. Six studies showed statistically significant improvements in sexual health, while three showed positive but non-significant effects. The summary effect size estimate was small SMD = 0.24 (95% confidence interval [CI]: 0.05 to 0.42, p = 0.01).Discussion: There is limited research on psychosocial interventions for sexual health in pelvic cancer patients. There are also limitations in the different pelvic cancer diagnoses examined. Commonly, the included articles examined physical function rather than the whole sexual health spectrum. The small effect sizes may in part be due to evaluation of psychosocial interventions by measuring physical dysfunction. Future research should broaden sexual health assessment tools and expand investigations to more cancer types.
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| 8. |
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| 9. |
- Barjesteh van Waalwijk van Doorn-Khosrovani, Sahar, et al.
(författare)
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PCM4EU and PRIME-ROSE : Collaboration for implementation of precision cancer medicine in Europe
- 2024
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Ingår i: Acta Oncologica. - 1651-226X .- 1651-226X. ; 63, s. 385-391
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the two European Union (EU)-funded projects, PCM4EU (Personalized Cancer Medicine for all EU citizens) and PRIME-ROSE (Precision Cancer Medicine Repurposing System Using Pragmatic Clinical Trials), we aim to facilitate implementation of precision cancer medicine (PCM) in Europe by leveraging the experience from ongoing national initiatives that have already been particularly successful. PATIENTS AND METHODS: PCM4EU and PRIME-ROSE gather 17 and 24 partners, respectively, from 19 European countries. The projects are based on a network of Drug Rediscovery Protocol (DRUP)-like clinical trials that are currently ongoing or soon to start in 11 different countries, and with more trials expected to be established soon. The main aims of both the projects are to improve implementation pathways from molecular diagnostics to treatment, and reimbursement of diagnostics and tumour-tailored therapies to provide examples of best practices for PCM in Europe. RESULTS: PCM4EU and PRIME-ROSE were launched in January and July 2023, respectively. Educational materials, including a podcast series, are already available from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients. ble from the PCM4EU website (http://www.pcm4eu.eu). The first reports, including an overview of requirements for the reimbursement systems in participating countries and a guide on patient involvement, are expected to be published in 2024. CONCLUSION: European collaboration can facilitate the implementation of PCM and thereby provide affordable and equitable access to precision diagnostics and matched therapies for more patients.
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| 10. |
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| 11. |
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| 12. |
- Ekberg, Sara, et al.
(författare)
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Impact of the COVID-19 pandemic on lymphoma incidence and short-term survival - a Swedish Lymphoma Register Study
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 164-168
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Tidskriftsartikel (refereegranskat)abstract
- Background & purpose: The COVID-19 pandemic posed a large challenge for healthcare systems across the world. Comprehensive data on the impact of the COVID-19 pandemic on incidence and mortality in lymphoma are lacking.Patients/methods: Using data from the Swedish lymphoma register, we compare incidence and 1-year survival of lymphoma patients in Sweden before (2017-2019) and during the pandemic (2020 and 2021).Results: Fewer patients were diagnosed with lymphomas during March-June 2020, but the annual incidence rates for 2020 and 2021 were similar to those of 2017-2019. A larger proportion of patients presented with stage IV disease during 2021. There were no differences in other base-line characteristics nor application of active treatment in pre-pandemic and pandemic years. One-year overall survival was not inferior among lymphoma patients during the pandemic years compared to pre-pandemic years i.e., 2017-2019.Interpretation: The COVID-19 pandemic had limited impact on the incidence and mortality of lymphoma in Sweden.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- 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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| 17. |
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| 18. |
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| 19. |
- Jonsson, Håkan, et al.
(författare)
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Age-specific differences in breast cancer treatment between screen-detected and non-screen-detected breast cancers in women aged 40-74 years at diagnosis in Sweden 2008-2017
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 552-556
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: We have recently demonstrated that screen-detected invasive breast cancers had more favourable tumour characteristics than non-screen-detected. The objective of the study was to analyse differences in breast cancer treatment between screen-detected and non-screen-detected cases by age at diagnosis, with and without adjustment for tumour (T) and nodal (N) status, within a nationwide, population-based mammography screening programme utilising register data.MATERIAL AND METHODS: Data spanning 2008-2017 were collected from the National Quality Register for Breast Cancer. Multivariable logistic regression analysis was used to estimate odds ratios and 95% confidence intervals for treatment disparities between screen-detected and non-screen-detected breast cancer.RESULTS: Among 46,481 women diagnosed with invasive breast cancer aged 40-74 and invited for mammography screening, significant differences in treatment were observed. Screen-detected cases showed higher likelihoods of partial mastectomy compared to mastectomy, endocrine therapy, and radiotherapy, whereas chemotherapy and antibody therapy were less likely compared to non-screen-detected cases. However, when adjusting for surgery type, screen-detected cases showed lower likelihoods of radiotherapy. Age at diagnosis significantly influenced treatment odds ratios, with interactions observed for all treatments except radiotherapy adjusted for surgery. Differences increased with age, except for endocrine therapy. Radiotherapy adjusted for surgery type showed no age-related interaction. Adjusting for T and N did not alter these patterns.INTERPRETATION: In general, screen-detected cases received less aggressive treatment, such as mastectomy, chemotherapy, and antibody therapy, compared to non-screen-detected cases. Disparities increased with age, except for endocrine therapy and radiotherapy adjusted for surgery. Differences persisted after adjusting for T and N, suggesting that these factors cannot solely explain the results.
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| 20. |
- Karihtala, Peeter, et al.
(författare)
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Clinical trials in older patients with cancer : typical challenges, possible solutions, and a paradigm of study design in breast cancer
- 2024
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 63, s. 441-447
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND AND PURPOSE: While the prevalence of older breast cancer patients is rapidly increasing, these patients are greatly underrepresented in clinical trials. We discuss barriers to recruitment of older patients to clinical trials and propose solutions on how to mitigate these challenges and design optimal clinical trials through the paradigm of IMPORTANT trial.PATIENTS AND METHODS: This is a narrative review of the current literature evaluating barriers to including older breast cancer patients in clinical trials and how mitigating strategies can be implemented in a pragmatic clinical trial. RESULTS: The recognized barriers can be roughly divided into trial design-related (e.g. the adoption of strict inclusion criteria, the lack of pre-specified age-specific analysis), patient-related (e.g. lack of knowledge, valuation of the quality-of-life instead of survival, transportation issues), or physician-related (e.g. concern for toxicity). Several strategies to mitigate barriers have been identified and should be considered when designing a clinical trial dedicated to older patients with cancer. The pragmatic, de-centralized IMPORTANT trial focusing on dose optimization of CDK4/6 -inhibitors in older breast cancer patients is a paradigm of a study design where different mitigating strategies have been adopted.INTERPRETATION: Because of the existing barriers, older adults in clinical trials are considerably healthier than the average older patients treated in clinical practice. Thus, the study results cannot be generalized to the older population seen in daily clinical practice. Broader inclusion/exclusion criteria, offering telehealth visits, and inclusion of patient-reported, instead of physician-reported outcomes may increase older patient participation in clinical trials.
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| 21. |
- Karihtala, Peeter, et al.
(författare)
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Clinical trials in older patients with cancer - typical challenges, possible solutions, and a paradigm of study design in breast cancer
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63:1, s. 441-447
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Forskningsöversikt (refereegranskat)abstract
- Background and purpose: While the prevalence of older breast cancer patients is rapidly increasing, these patients are greatly underrepresented in clinical trials. We discuss barriers to recruitment of older patients to clinical trials and propose solutions on how to mitigate these challenges and design optimal clinical trials through the paradigm of IMPORTANT trial.Patients and methods: This is a narrative review of the current literature evaluating barriers to including older breast cancer patients in clinical trials and how mitigating strategies can be implemented in a pragmatic clinical trial.Results: The recognized barriers can be roughly divided into trial design -related (e.g . the adoption of strict inclusion criteria, the lack of pre-specified age-specific analysis), patient-related (e.g . lack of knowledge, valuation of the quality-of-life instead of survival, transportation issues), or physician-related (e.g . concern for toxicity). Several strategies to mitigate barriers have been identified and should be considered when designing a clinical trial dedicated to older patients with cancer. The pragmatic, de-centralized IMPORTANT trial focusing on dose optimization of CDK4/6 -inhibitors in older breast cancer patients is a paradigm of a study design where different mitigating strategies have been adopted.Interpretation: Because of the existing barriers, older adults in clinical trials are considerably healthier than the average older patients treated in clinical practice. Thus, the study results cannot be generalized to the older population seen in daily clinical practice. Broader inclusion/exclusion criteria, offering telehealth visits, and inclusion of patient -reported, instead of physician -reported outcomes may increase older patient participation in clinical trials.
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| 22. |
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| 23. |
- Kinos, Sampsa, et al.
(författare)
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Detailed analysis of metastatic colorectal cancer patients who developed cardiotoxicity on another fluoropyrimidine and switched to S-1 treatment (subgroup analysis of the CardioSwitch-study)
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 248-258
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: The CardioSwitch-study demonstrated that patients with solid tumors who develop cardiotoxicity on capecitabine or 5-fluorouracil (5-FU) treatment can be safely switched to S-1, an alternative fluoropyrimidine (FP). In light of the European Medicines Agency approval of S-1 in metastatic colorectal cancer (mCRC), this analysis provides more detailed safety and efficacy information, and data regarding metastasectomy and/or local ablative therapy (LAT), on the mCRC patients from the original study.Materials and methods: This retrospective cohort study was conducted at 12 European centers. The primary endpoint was recurrence of cardiotoxicity after switch. For this analysis, safety data are reported for 78 mCRC patients from the CardioSwitch cohort (N = 200). Detailed efficacy and outcomes data were available for 66 mCRC patients.Results: Data for the safety of S-1 in mCRC patients were similar to the original CardioSwitch cohort and that expected for FP-based treatment, with no new concerns. Recurrent cardiotoxicity (all grade 1) with S-1-based treatment occurred in 4/78 (5%) mCRC patients; all were able to complete FP treatment. Median progression-free survival from initiation of S-1-based treatment was 9.0 months and median overall survival 26.7 months. Metastasectomy and/or LAT was performed in 33/66 (50%) patients, and S-1 was successfully used in recommended neoadjuvant/conversion or adjuvant-like combination regimens and schedules as for standard FPs.Interpretation: S-1 is a safe and effective FP alternative when mCRC patients are forced to discontinue 5-FU or capecitabine due to cardiotoxicity and can be safely used in the standard recommended regimens, settings, and schedules.
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| 24. |
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| 25. |
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| 26. |
- Paakkola, Nelly-Maria, et al.
(författare)
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Area-based disparities in non-small-cell lung cancer survival
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 146-153
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the Nordic countries, universal healthcare access has been effective in reducing socioeconomic disparities in non-small-cell lung cancer (NSCLC) management. However, other factors, such as proximity to healthcare facilities, may still affect access to care. This study aimed at investigating the influence of residential area on NSCLC survival.METHODS: This population-based study utilized hospital records to identify NSCLC patients who underwent their initial treatment at Vaasa Central Hospital between January 1, 2016, and December 31, 2020. Patients were categorized based on their postal codes into urban areas (≤50 km from the hospital) and rural areas (>50 km from the hospital). Survival rates between these two groups were compared using Cox regression analysis.RESULTS: A total of 321 patients were included in the study. Patients residing in rural areas (n = 104) exhibited poorer 12-month survival rates compared to their urban counterparts (n = 217) (unadjusted Hazard Ratio [HR]: 1.38; 95% Confidence Interval [CI]: 1.01-1.89; p = 0.042). After adjusting for factors such as performance status, frailty, and stage at diagnosis in a multivariate Cox regression model, the adjusted HR increased to 1.47 (95% CI: 1.07-2.01; p = 0.017) for patients living in rural areas compared to those in urban areas.INTERPRETATION: The study findings indicate that the distance to the hospital is associated with increased lung cancer mortality. This suggests that geographical proximity may play a crucial role in the disparities observed in NSCLC survival rates. Addressing these disparities should involve strategies aimed at improving healthcare accessibility, particularly for patients residing in rural areas, to enhance NSCLC outcomes and reduce mortality.
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| 27. |
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| 28. |
- 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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| 29. |
- Zarei, Maryam, et al.
(författare)
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Accuracy of gross tumour volume delineation with [68Ga]-PSMA-PET compared to histopathology for high-risk prostate cancer
- 2024
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Ingår i: Acta Oncologica. - : MJS Publishing, Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63, s. 503-510
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The delineation of intraprostatic lesions is vital for correct delivery of focal radiotherapy boost in patients with prostate cancer (PC). Errors in the delineation could translate into reduced tumour control and potentially increase the side effects. The purpose of this study is to compare PET-based delineation methods with histopathology.MATERIALS AND METHODS: The study population consisted of 15 patients with confirmed high-risk PC intended for prostatectomy. [68Ga]-PSMA-PET/MR was performed prior to surgery. Prostate lesions identified in histopathology were transferred to the in vivo [68Ga]-PSMA-PET/MR coordinate system. Four radiation oncologists manually delineated intraprostatic lesions based on PET data. Various semi-automatic segmentation methods were employed, including absolute and relative thresholds, adaptive threshold, and multi-level Otsu threshold.RESULTS: The gross tumour volumes (GTVs) delineated by the oncologists showed a moderate level of interobserver agreement with Dice similarity coefficient (DSC) of 0.68. In comparison with histopathology, manual delineations exhibited the highest median DSC and the lowest false discovery rate (FDR) among all approaches. Among semi-automatic approaches, GTVs generated using standardized uptake value (SUV) thresholds above 4 (SUV > 4) demonstrated the highest median DSC (0.41), with 0.51 median lesion coverage ratio, FDR of 0.66 and the 95th percentile of the Hausdorff distance (HD95%) of 8.22 mm.INTERPRETATION: Manual delineations showed a moderate level of interobserver agreement. Compared to histopathology, manual delineations and SUV > 4 exhibited the highest DSC and the lowest HD95% values. The methods that resulted in a high lesion coverage were associated with a large overestimation of the size of the lesions.
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| 30. |
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| 31. |
- Aamand Grabau, Dorthe, et al.
(författare)
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The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the choice of antibody and method of heat-induced epitope retrieval - prognostic implications?
- 2013
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Ingår i: Acta Oncologica. - : Informa Healthcare. - 0284-186X .- 1651-226X. ; 52:8, s. 1657-1666
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Tidskriftsartikel (refereegranskat)abstract
- Background. Oestrogen receptor (ER) status is important for the choice of systemic treatment of breast cancer patients. However, most data from randomised trials on the effect of adjuvant endocrine therapy according to ER status are based on the cytosol methods. Comparisons with immunohistochemical methods have given similar results. The aim of the present study was to examine whether different ER antibodies and heat-induced epitope retrieval (HIER) methods influence the prevalence of ER-positivity in primary breast cancer. Material and methods. This study is based on patients included in a clinical trial designed to compare the effect of two years of adjuvant tamoxifen versus no adjuvant systemic treatment in premenopausal women. From 1986 to 1991, 564 patients from two study centres in Sweden were enrolled and randomised. Patients were randomised independently of ER status. In the present study, ER status was assessed on tissue microarrays with the three different ER antibody/HIER combinations: 1D5 in citrate pH 6 (n = 390), SP1 in Tris pH 9 (n = 390) and PharmDx in citrate pH 6 (n = 361). Results. At cut-offs of 1% and 10%, respectively, the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%). At these cut-offs, patients in the discordant groups (SP1-positive and 1D5-negative) seem to have a prognosis intermediate between those of the double-positive and double-negative groups. Comparison with the ER status determined by the cytosol-based methods in the discordant group also showed an intermediate pattern. The repeatability was good for all antibodies and cut-offs, with overall agreement andgt;= 93%. Conclusion. The present study shows that the choice of antibody and HIER method influences the prevalence of ER-positivity. We suggest that this be taken into consideration when choosing a cut-off for clinical decision making.
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| 32. |
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| 33. |
- Abdulla, Maysaa, et al.
(författare)
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A population-based study of cellular markers in R-CHOP treated diffuse large B-cell lymphoma patients
- 2016
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 55:9-10, s. 1126-1131
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To determine the prognostic significance of co-expression of MYC, BCL-2 and BCL-6 proteins in combination with other biomarkers and clinical characteristics within a population-based cohort of diffuse large B-cell lymphoma (DLBCL) patients uniformly treated with R-CHOP.Patients and methods: The immunohistochemical (IHC) expression of CD10, BCL-2, BCL-6, MUM1, MYC, CD5, CD30, Ki-67 and p53 was evaluated in a retrospective, population-based study comprising 188 DLBCL patients treated with R-CHOP and diagnosed in Sweden between 2002 and 2012.Results: Patients had a median age at diagnosis of 64 years (26-85 years) with a male:female ratio of 1.4:1. Approximately half (52%) of the patients presented with an International Prognostic Index (IPI) age adjusted (IPIaa)2. Median follow-up time was 51 months (range 0.4-158) and the five-year lymphoma-specific survival (LSS) was 76%, five-year overall survival (OS) was 65% and five-year progression-free survival (PFS) was 61%. A high Ki-67 value was found in 59% of patients, while p53 overexpression was detected in 12% of patients and MYC, BCL-2 and BCL-6 expression were detected in 42%, 55% and 74% of patients, respectively. IPIaa2 (p=0.002), Ki-6770% (p=0.04) and p53 overexpression50% (p=0.02) were associated with inferior LSS and OS. Co-expression of both MYC (>40%) and BCL-2 (>70%) proteins was detected in 27% of patients and correlated with a significantly inferior LSS (p=0.0002), OS (p=0.009) and PFS (p=0.03). In addition, triple expression of MYC, BCL-2 and BCL-6, also correlated with a significantly inferior LSS (p=0.02).Conclusion: Concurrent expression of MYC and BCL-2 proteins, as detected by IHC, was strongly associated with an inferior survival in DLBCL patients treated with R-CHOP. Other markers affecting survival were triple expression of MYC, BCL-2 and BCL-6, IPIaa, high Ki-67 and p53 overexpression.
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| 34. |
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| 35. |
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| 36. |
- Abdulla, Maysaa, et al.
(författare)
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PD-L1 and IDO1 are potential targets for treatment in patients with primary diffuse large B-cell lymphoma of the CNS
- 2021
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Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 60:4, s. 531-538
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundProgrammed cell death 1 (PD-1) and its ligands PD-L1 and PD-L2, as well as Indoleamine 2,3-deoxygenase (IDO1) can be expressed both by tumor and microenvironmental cells and are crucial for tumor immune escape. We aimed to evaluate the role of PD-1, its ligands and IDO1 in a cohort of patients with primary diffuse large B-cell lymphoma of the CNS (PCNSL).Material and methodsTissue microarrays (TMAs) were constructed in 45 PCNSL cases. RNA extraction from whole tissue sections and RNA sequencing were successfully performed in 33 cases. Immunohistochemical stainings for PD-1, PD-L1/paired box protein 5 (PAX-5), PD-L2/PAX-5 and IDO1, and Epstein-Barr virus encoding RNA (EBER) in situ hybridization were analyzed.ResultsHigh proportions of PD-L1 and PD-L2 positive tumor cells were observed in 11% and 9% of cases, respectively. High proportions of PD-L1 and PD-L2 positive leukocytes were observed in 55% and 51% of cases, respectively. RNA sequencing revealed that gene expression of IDO1 was high in patients with high proportion of PD-L1 positive leukocytes (p = .01). Protein expression of IDO1 in leukocytes was detected in 14/45 cases, in 79% of these cases a high proportion of PD-L1 positive leukocytes was observed. Gene expression of IDO1 was high in EBER-positive cases (p = .0009) and protein expression of IDO1 was detected in five of six EBER-positive cases.ConclusionOur study shows a significant association between gene and protein expression of IDO1 and protein expression of PD-L1 in the tumor microenvironment of PCNSL, possibly of importance for prediction of response to immunotherapies.
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| 37. |
- Adami, HO
(författare)
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The prostate cancer pseudo-epidemic
- 2010
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 49:3, s. 298-304
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 38. |
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| 39. |
- Adolfsson, J
(författare)
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Screening for prostate cancer - will we ever know?
- 2010
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Ingår i: Acta oncologica (Stockholm, Sweden). - : Informa UK Limited. - 1651-226X .- 0284-186X. ; 49:3, s. 275-277
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 40. |
- Adrian, Gabriel, et al.
(författare)
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Importance of tumor volume, overall treatment time and fractionation sensitivity for p16-positive and p16-negative oropharyngeal tumors
- 2023
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 62:11, s. 1375-1383
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Analyses of clinical outcomes following radiotherapy (RT) have advanced our understanding of fundamental radiobiological characteristics in head and neck squamous cell carcinoma (HNSCC). Low fractionation sensitivity appears to be a common feature, as well as susceptibility to changes in overall treatment time (OTT). Large tumors should be harder to cure if a successful RT requires the sterilization of all clonogenic cells. Congruently, primary tumor volume has proven to be an important parameter. However, most findings come from an era when p16-negative HNSCC was the dominant tumor type. HPV-associated, p16-positive, oropharyngeal tumors (OPSCC) are more radiosensitive and have better outcome. The current study aims to investigate the role of primary tumor volume, OTT and estimate α/β-ratio for p16-positive OPSCC, and to quantify the differences in radiosensitivity depending on p16-status.METHODS: A cohort of 523 patients treated with RT was studied using a tumor control probability (TCP)-model that incorporates primary tumor volume (V) raised to an exponent c, OTT and α/β-estimation. The significance of V was also investigated in Cox-regression models.RESULTS: In the p16-positive cohort (n = 433), the volume exponent c was 1.44 (95%CI 1.06-1.91), compared to 0.90 (0.54-1.32) for p16-negative tumors (n = 90). Hazard ratios per tumor volume doubling were 2.37 (1.72-3.28) and 1.83 (1.28-2.62) for p16-positive and p16-negative, respectively. The estimated α/β-ratio was 9.7 Gy (-2.3-21.6), and a non-significant daily loss of 0.30 Gy (-0.17-0.92) was found. An additional dose of 6.8 Gy (interquartile range 4.8-9.1) may theoretically counteract the more radioresistant behavior of p16-negative tumors.CONCLUSION: Primary tumor volume plays a crucial role in predicting local tumor response, particularly in p16-positive OPSCC. The estimated α/β-ratio for p16-positive oropharyngeal tumors aligns with previous HNSCC studies, whereas the impact of prolonged OTT was slightly less than previously reported. The differences in radiosensitivity depending on p16-status were quantified. The findings should be validated in independent cohorts.
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| 41. |
- Ahlin, Cecilia, et al.
(författare)
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Aberrant expression of cyclin E in low-risk node negative breast cancer
- 2008
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 47:8, s. 1539-1545
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Tidskriftsartikel (refereegranskat)abstract
- Background. Cyclin E is a cell cycle regulatory protein which occurs in G1, peaks in late G1 and is degraded in early S-phase. Cyclin E overexpression appears to be an independent prognostic factor for overall survival in breast cancer. Material and Methods. Nuclear cyclin A is a reliable marker for S-and G2-phases. Consequently, aberrant expression of cyclin E can be detected by simultaneous immunostainings for cyclin A and cyclin E. Studies have shown that aberrant cyclin E might provide additional prognostic information compared to that of cyclin E alone. This study aimed to investigate cyclin E and aberrant cyclin E expression in low-risk node negative breast cancer. We compared women that died from their breast cancer (n=17) with women free from relapse>8 years after initial diagnosis (n=24). All women had stage I, low risk breast cancer. The groups were matched regarding tumour size, receptor status, adjuvant chemotherapy and tumour differentiation. Tumour samples were analysed regarding expression of cyclin A, cyclin E and double-stained tumour cells using immunoflourescence staining and digital microscopy. Results. No differences were seen regarding expression of cyclin E or aberrant cyclin E in cases compared to controls. Discussion. We conclude that neither cyclin E nor aberrant cyclin E is a prognostic factor in low-risk node negative breast cancer patients.
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| 42. |
- Ahlström, Håkan, et al.
(författare)
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An experimental model for pharmacokinetic studies of monoclonal antibodies in human colonic cancer
- 1987
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 26:6, s. 447-451
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Tidskriftsartikel (refereegranskat)abstract
- An experimental model consisting of athymic rats carrying human colonic tumours from cell line LS 174T in both hind legs was used. 125I-labelled anti-carcinoembryonic antigen (anti-CEA) monoclonal antibodies were injected intra-arterially (i.a.), either alone (21 rats) or together with degradable starch microspheres (6 rats). As a control, an irrelevant antibody was injected i.a., alone (6 rats) or together with microspheres (3 rats). An intra-arterial injection was given on the side bearing one tumour in each rat, while the contralateral tumour served as an 'intravenous' control. The rats were submitted to external gamma measurements daily for four days. On the fourth day they were killed and pieces from the tumours and from various organs were examined by in vitro measurements. The results indicate strong expression of CEA in LS 174T cells grafted to athymic rats. No lasting enhancement of the tumour uptake was achieved by intra-arterial injection of antibodies as compared with the control tumours.
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| 43. |
- Ahlström, Håkan, et al.
(författare)
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Enhanced uptake of intra-arterially injected anti-CEA monoclonal antibodies in human colonic cancer after mannitol infusion in an experimental model
- 1987
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 26:6, s. 453-458
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Tidskriftsartikel (refereegranskat)abstract
- In a previous report athymic rats carrying transplanted human colonic tumours from cell line LS 174T in both hind legs were injected intra-arterially (i.a.) with 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies. The i.a. injection was given on one side bearing a tumour in each rat, while the contralateral tumour served as an 'intravenous' control. In the same experimental model and treated in the same way, 10 rats were injected i.a. with anti-CEA monoclonal antibodies after an i.a. mannitol infusion. In both groups of rats external gamma measurements were performed daily for four days. On the fourth day the rats were killed and pieces of the tumours and of various organs were weighed and the activity was determined with a gamma-counter. The tumour uptake of antibodies was significantly enhanced after mannitol infusion.
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| 44. |
- Ahlström, Håkan, et al.
(författare)
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The spatial distribution of parenterally administered monoclonal antibodies against CEA in a human colorectal tumour xenograft
- 1989
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Ingår i: Acta Oncologica. - 0284-186X .- 1651-226X. ; 28:1, s. 81-86
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Tidskriftsartikel (refereegranskat)abstract
- A recently developed experimental model consisting of athymic rats carrying human colonic tumours from the cell line LS 174 T in both hind legs was used. 125I-labelled anti-carcinoembryonic (anti-CEA) monoclonal antibodies were injected either intra-arterially after a bolus injection of mannitol, or intra-peritoneally with or without mannitol. On the fourth day the rats were killed and pieces from the tumours and various organs were measured in a well scintillation counter. Tumour pieces were then submitted to autoradiography and immunohistochemistry for examination of the antibody distribution at the cellular level. In all examined tumours injected with anti-CEA antibodies, most of the antibodies were located in the periphery close to fibrovascular septa. It appears, in addition to the specificity of the antibody for the CEA, that the tumour vascular permeability and anatomy are of utmost importance for tumour targeting in this experimental model with the particular antibody used.
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| 45. |
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| 46. |
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| 47. |
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| 48. |
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| 49. |
- Al-Olama, Mohamed, et al.
(författare)
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The peptide AF-16 decreases high interstitial fluid pressure in solid tumors.
- 2011
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Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X.
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background. The high interstitial fluid pressure (IFP) in solid tumors restricts the access to nutrients, oxygen and drugs. Material and methods. We investigated the ability of the peptide AF-16, involved in water and ion transfer through cell membranes, to lower the IFP in two different solid rat mammary tumors, one chemically induced, slowly growing, and the other transplantable, and rapidly progressing having high cellularity. AF-16 was administered either in the tumor capsule, intranasally or intravenously. The IFP was measured by a miniature fiber optic device. Results. AF-16 significantly lowered the IFP in both the slowly and the rapidly progressing tumors, whether administrated locally or systemically. The AF-16 induced IFP reduction was maximal after 90 min, lasted at least 3 h, and returned to pretreatment levels in less than 24 h. Topical AF-16 transiently reduced the IFP in the DMBA tumors from 17.7 ± 4.2 mmHg to 8.6 ± 2.1 mmHg. Conclusion. We conclude that AF-16 transiently and reversibly lowered the high IFP in solid tumors during a few hours, which might translate into improved therapeutic efficacy.
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