| 1. |
- Bahadoer, Renu R., et al.
(author)
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Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO) : a randomised, open-label, phase 3 trial
- 2021
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In: The Lancet Oncology. - : Elsevier. - 1470-2045 .- 1474-5488. ; 22:1, s. 29-42
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Journal article (peer-reviewed)abstract
- Background Systemic relapses remain a major problem in locally advanced rectal cancer. Using short-course radiotherapy followed by chemotherapy and delayed surgery, the Rectal cancer And Preoperative Induction therapy followed by Dedicated Operation (RAPIDO) trial aimed to reduce distant metastases without compromising locoregional control. Methods In this multicentre, open-label, randomised, controlled, phase 3 trial, participants were recruited from 54 centres in the Netherlands, Sweden, Spain, Slovenia, Denmark, Norway, and the USA. Patients were eligible if they were aged 18 years or older, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, had a biopsy-proven, newly diagnosed, primary, locally advanced rectal adenocardnoma, which was classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for chemotherapy, and could be assessed for staging within S weeks before randomisation. Eligible participants were randomly assigned (1:1), using a management system with a randomly varying block design (each block size randomly chosen to contain two to four allocations), stratified by centre, ECOG performance status, cT stage, and cN stage, to either the experimental or standard of care group. All investigators remained masked for the primary endpoint until a prespecified number of events was reached. Patients allocated to the experimental treatment group received short-course radiotherapy (5 x 5 Gy over a maximum of 8 days) followed by six cycles of CAPDX chemotherapy (capecitabine 1000 mg/m(2) orally twice daily on days 1-14, oxaliplatin 130 mg/m(2) intravenously on day 1, and a chemotherapy-free interval between days 15-21) or nine cycles of FOLFOX4 (oxaliplatin 85 mg/m(2) intravenously on day 1, leucovorin [folinic acid] 200 mg/m 2 intravenously on days 1 and 2, followed by bolus fluorouracil 400 mg/m(2) intravenously and fluorouracil 600 mg/m 2 intravenously for 22 h on days 1 and 2, and a chemotherapy-free interval between days 3-14) followed by total mesorectal excision. Choice of CAPDX or FOLFOX4 was per physician discretion or hospital policy. Patients allocated to the standard of care group received 28 daily fractions of 1.8 Gy up to 50.4 Gy or 25 fractions of 2.0 Gy up to 50.0 Gy (per physician discretion or hospital policy), with concomitant twice-daily oral capecitabine 825 mg/m(2) followed by total mesorectal excision and, if stipulated by hospital policy, adjuvant chemotherapy with eight cycles of CAPDX or 12 cycles of FOLFOX4. The primary endpoint was 3-year disease-related treatment failure, defined as the first occurrence of locoregional failure, distant metastasis, new primary colorectal tumour, or treatment-related death, assessed in the intention-to-treat population. Safety was assessed by intention to treat. This study is registered with the EudraCT, 2010-023957-12, and ClinicalTrials.gov , NCT01558921, and is now complete. Findings Between June 21,2011, and June 2,2016,920 patients were enrolled and randomly assigned to a treatment, of whom 912 were eligible (462 in the experimental group; 450 in the standard of care group). Median follow-up was 4.6 years (IQR 3.5-5.5). At 3 years after randomisation, the cumulative probability of disease-related treatment failure was 23.7% (95% CI 19.8-27.6) in the experimental group versus 30.4% (26.1-34.6) in the standard of care group (hazard ratio 0.75, 95% CI 0.60-0-95; p=0-019). The most common grade 3 or higher adverse event during preoperative therapy in both groups was diarrhoea (81 [18%] of 460 patients in the experimental group and 41 [9%] of 441 in the standard of care group) and neurological toxicity during adjuvant chemotherapy in the standard of care group (16 [9%] of 187 patients). Serious adverse events occurred in 177 (38%) of 460 participants in the experimental group and, in the standard of care group, in 87 (34%) of 254 patients without adjuvant chemotherapy and in 64 (34%) of 187 with adjuvant chemotherapy. Treatment-related deaths occurred in four participants in the experimental group (one cardiac arrest, one pulmonary embolism, two infectious complications) and in four participants in the standard of care group (one pulmonary embolism, one neutropenic sepsis, one aspiration, one suicide due to severe depression). Interpretation The observed decreased probability of disease-related treatment failure in the experimental group is probably indicative of the increased efficacy of preoperative chemotherapy as opposed to adjuvant chemotherapy in this setting. Therefore, the experimental treatment can be considered as a new standard of care in high-risk locally advanced rectal cancer.
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| 2. |
- Björeland, Ulrika, et al.
(author)
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Impact of neoadjuvant androgen deprivation therapy on magnetic resonance imaging features in prostate cancer before radiotherapy
- 2021
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In: Physics and Imaging in Radiation Oncology. - : Elsevier. - 2405-6316. ; 17, s. 117-123
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Journal article (peer-reviewed)abstract
- Background and purpose: In locally advanced prostate cancer (PC), androgen deprivation therapy (ADT) in combination with whole prostate radiotherapy (RT) is the standard treatment. ADT affects the prostate as well as the tumour on multiparametric magnetic resonance imaging (MRI) with decreased PC conspicuity and impaired localisation of the prostate lesion. Image texture analysis has been suggested to be of aid in separating tumour from normal tissue. The aim of the study was to investigate the impact of ADT on baseline defined MRI features in prostate cancer with the goal to investigate if it might be of use in radiotherapy planning.Materials and methods: Fifty PC patients were included. Multiparametric MRI was performed before, and three months after ADT. At baseline, a tumour volume was delineated on apparent diffusion coefficient (ADC) maps with suspected tumour content and a reference volume in normal prostatic tissue. These volumes were transferred to MRIs after ADT and were analysed with first-order -and invariant Haralick -features.Results: At baseline, the median value and several of the invariant Haralick features of ADC, showed a significant difference between tumour and reference volumes. After ADT, only ADC median value could significantly differentiate the two volumes.Conclusions: Invariant Haralick -features could not distinguish between baseline MRI defined PC and normal tissue after ADT. First-order median value remained significantly different in tumour and reference volumes after ADT, but the difference was less pronounced than before ADT.
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| 3. |
- Blomqvist, Lennart, 1947, et al.
(author)
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Arachidonic acid-induced platelet aggregation and acetylsalicylic acid treatment during pregnancy in women with recurrent miscarriage, a post hoc study
- 2022
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In: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 33:2, s. 278-284
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Journal article (peer-reviewed)abstract
- In this post hoc study, arachidonic acid (AA)-induced platelet aggregation during pregnancy with and without acetylsalicylic acid (ASA) treatment was studied in 323 women with unexplained recurrent first-trimester miscarriage and in 59 healthy women with normal pregnancies. All women had normal AA-induced platelet aggregation in the non-pregnant state. Women with recurrent miscarriage were treated with 75 mg ASA or placebo daily. AA-induced platelet aggregation was measured with multiple electrode impedance aggregometry and presented in units (U), where 1 U = 10 aggregation units x minutes. There were no significant differences in platelet aggregation between placebo-treated women with recurrent miscarriage and healthy women. The mean differences were -0.7 (95%CI; -7.0; 5.6) U in the non-pregnant state, 3.8 (95%CI; -4.6; 12.2) U during the late first trimester and 1.7 (95%CI; -6.7; 10.3) U and 4.1 (95%CI; -3.9; 12.0) U during the early and late third trimester, respectively. ASA reduced platelet aggregation by median -84.0% (Q1; Q3; -89.8; -76.3), -79.9% (-84.7; -69.2) and -75.7% (-83.5; -49.5), respectively, during pregnancy. The degree of inhibition by ASA decreased during the third trimester (p < .0001). There were two (1.9%) complete non-responders to ASA and 32.1% with a partial response. The rate of subsequent miscarriage was not affected by ASA, which did not seem to influence the rate of early miscarriage if treatment was initiated when a viable pregnancy was detectable by ultrasound.
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| 4. |
- Blomqvist, Lennart, et al.
(author)
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Gadolinium in Medical Imaging—Usefulness, Toxic Reactions and Possible Countermeasures : A Review
- 2022
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In: Biomolecules. - : MDPI. - 2218-273X. ; 12:6
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Research review (peer-reviewed)abstract
- Gadolinium (Gd) is one of the rare-earth elements. The properties of its trivalent cation (Gd3+) make it suitable to serve as the central ion in chelates administered intravenously to patients as a contrast agent in magnetic resonance imaging. Such Gd-chelates have been used for more than thirty years. During the past decades, knowledge has increased about potential harmful effects of Gd-chelates in patients with severe renal dysfunction. In such patients, there is a risk for a potentially disabling and lethal disease, nephrogenic systemic fibrosis. Restricting the use of Gd-chelates in persons with severely impaired renal function has decreased the occurrence of this toxic effect in the last decade. There has also been an increasing awareness of Gd-retention in the body, even in patients without renal dysfunction. The cumulative number of doses given, and the chemical structure of the chelate given, are factors of importance for retention in tissues. This review describes the chemical properties of Gd and its medically used chelates, as well as its toxicity and potential side effects related to injection of Gd-chelates.
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| 5. |
- Blomqvist, Lennart K., et al.
(author)
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Gadolinium
- 2022. - 5
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In: Handbook on the toxicology of metals. - : Elsevier. - 9780128229460 ; , s. 267-274
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Book chapter (peer-reviewed)abstract
- Gadolinium (Gd) belongs to the rare-earth elements. Depending on the temperature, Gd is either ferromagnetic or paramagnetic. Gadolinium obtained its name from Johan Gadolin, the Finnish chemist who discovered gadolinite, a mineral that contains gadolinium. The specific properties of Gd make it suitable for certain applications in nuclear reactors as well as in medicine being the base for a chelate administered to patients as a contrast agent in magnetic resonance imaging. Such Gd chelates have been used for more than 30 years. During the past decades, there has been increasing knowledge about the potentially harmful effects of Gd chelates in patients with severe renal dysfunction. In such patients, there is a risk for a potentially life-threatening disease, nephrogenic systemic fibrosis. Precautions, restricting the use of Gd chelates in persons with severely impaired renal function have drastically decreased the occurrence of nephrogenic systemic fibrosis in the last decade. There has also been an increasing awareness of the fact that there is Gd deposition in the body even in patients without renal dysfunction and that this deposition is related partly to the cumulative number of doses given but also the chemical structure of the chelate. In this chapter, the physical and chemical properties of Gd and its related chelates, methods for detection, industrial and medical applications, human exposures, toxicity as well as a further description of potential side effects related to injection of Gd chelates are described.
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| 6. |
- Blomqvist, Lennart, 1947, et al.
(author)
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Preconceptual thyroid peroxidase antibody positivity in women with recurrent pregnancy losses may contribute to an increased risk for another miscarriage.
- 2023
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In: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 98:2, s. 259-269
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Journal article (peer-reviewed)abstract
- To investigate preconceptual thyroid peroxidase antibody (TPO-ab) positivity and/or thyroid stimulating hormone (TSH) levels in the upper range of normal as risk factors for recurrent unexplained first-trimester miscarriage.A post-hoc study of a randomized trial, in which acetylsalicylic acid did not affect the risk of a new miscarriage.Women (n=483) with at least three unexplained recurrent first-trimester miscarriages investigated at a Swedish secondary referral center.The levels of TPO-ab and TSH were determined before pregnancy. The occurrence of a new first-trimester miscarriage was analyzed by logistic regression with adjustments when applicable, for age, number of previous miscarriages, obesity and the investigated covariates levels of TPO-ab and TSH.Including all first trimester miscarriages, odds ratio (OR) according to presence of TPO-ab was 1.60 (95% confidence interval [CI]; 0.99-2.57), after adjustment 1.54 (95% CI; 0.94-2.53). Very early (biochemical) pregnancy losses occurred more often in women with than without preconceptual TPO-ab (6.8% vs. 2.0%), OR 3.51 (95% CI; 1.15-10.71), after adjustment 2.91 (95% CI; 0.91-9.29). There was no association between TSH in the upper range of normal and a new miscarriage, adjusted OR 0.76 (95% CI; 0.32-1.83). A prediction model for a new miscarriage included number of previous miscarriages, woman's age and presence of TPO-ab.In women with at least three recurrent unexplained pregnancy losses, the presence of TPO-ab may contribute to an increased risk of a first-trimester miscarriage, possibly more pronounced in very early pregnancy. TSH levels 2.5-4.0 mU/L do not seem to increase the miscarriage risk.
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| 7. |
- Elliot, Anders H., et al.
(author)
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Pretreatment MRI in Primary Rectal Cancer as a Predictor for Oncological Outcomes After Surgery for Local Recurrence
- 2021
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In: Anticancer Research. - : Anticancer Research USA Inc.. - 0250-7005 .- 1791-7530. ; 41:5, s. 2459-2465
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Journal article (peer-reviewed)abstract
- Background/Aim: For patients with locally recurrent rectal cancer (LRRC) extensive surgery is often the only curative option and patient selection is crucial. This study aimed to investigate whether magnetic resonance imaging (MRI) characteristics of the primary tumour can predict oncological outcome after surgery for locally recurrent rectal cancer (LRRC). Patients andMethods: All patients undergoing surgery for LRRC with a curative intent at the Karolinska University Hospital 2003-2013 were included. MRI examinations of the primary tumour were re-evaluated.Results: In total, 54 patients were included. A tumour volume decrease of <70% after preoperative radiotherapy or chemoradiotherapy (C)RT for the primary tumour was correlated with a lower proportion of R0 resection of the LRRC (OR=0.07, 95% CI=0.01-0.84). No association between MRI characteristics of the primary tumour and prognosis after LRRC surgery was found.Conclusion: Long-term outcomes after surgery for LRRC were not significantly associated with MRI characteristics of the index tumour. However, factors associated with increased risk of R1 resection of LRRC were identified.
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| 8. |
- Gulevski, Stephanie, et al.
(author)
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MRI morphological characteristics of lymph nodes in anal squamous cell carcinoma
- 2024
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In: Abdominal Radiology. - 2366-004X. ; 49:4, s. 1042-1050
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Journal article (peer-reviewed)abstract
- ObjectivesPre-treatment staging of anal squamous cell carcinoma (ASCC) includes pelvic MRI and [18F]-fluorodeoxyglucose positron emission tomography with computed tomography (PET-CT). MRI criteria to define lymph node metastases (LNMs) in ASCC are currently lacking. The aim of this study was to describe the morphological characteristics of lymph nodes (LNs) on MRI in ASCC patients with PET-CT-positive LNs.MethodsASCC patients treated at Skåne University Hospital between 2009 and 2017 were eligible for inclusion if at least one positive LN according to PET-CT and a pre-treatment MRI were present. All PET-CT-positive LNs and PET-CT-negative LNs were retrospectively identified on baseline MRI. Each LN was independently classified according to pre-determined morphological characteristics by two radiologists blinded to clinical patient information.ResultsSixty-seven ASCC patients were included, with a total of 181 PET-CT-positive LNs identified on baseline MRI with a median short-axis diameter of 9.0 mm (range 7.5–12 mm). MRI morphological characteristics of PET-CT-positive LNs included regular contour (87%), round shape (89%), and homogeneous signal intensity on T2-weighed images (67%). An additional 78 PET-CT-negative LNs were identified on MRI. These 78 LNs had a median size of 6.8 mm (range 5.5–8.0 mm). The majority of PET-CT-negative LNs had a regular contour, round shape, and a homogeneous signal that was congruent to the primary tumor.ConclusionsThere are MRI-specific morphological characteristics for pelvic LNs in ASCC. PET-CT-positive and negative LNs share similar morphological features apart from size, with PET-CT-positive LNs being significantly larger. Further studies are needed to determine discrimination criteria for LNM in ASCC.
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| 9. |
- Inkiläinen, Aapo, et al.
(author)
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Patient-reported outcome measures of abdominal wall morbidity after flank incision for open partial nephrectomy
- 2021
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In: BJU International. - : John Wiley & Sons. - 1464-4096 .- 1464-410X. ; 128:4, s. 497-503
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Journal article (peer-reviewed)abstract
- Objective: To compare patient-reported outcome measures in patients with and without abdominal wall complications after open partial nephrectomy (OPN) via flank incision.Patients and Methods: Patient-reported outcome measures were collected in 2017 from all patients operated on with OPN via flank incision between 2004 and 2016 in Västerbotten County, Sweden. Patients were mailed the ventral hernia pain questionnaire (VHPQ) and an abdominal wall asymmetry (AWA) questionnaire to evaluate postoperative AWA, attributed to bulge or incisional hernia. Demographic and follow-up data were retrieved from patient records.Results: A total of 198 patients were eligible for the study, and 146 questionnaires were returned (74%). Forty-five patients (31%) reported postoperative AWA and 27 (18%) reported ongoing pain. Three patients who reported AWA had a known incisional hernia. Pain and abdominal wall stiffness were more common in patients with AWA than in those without (P < 0.01 and P < 0.01, respectively). Of the 45 patients with AWA, 25 (56%) reported this as being negative cosmetically and 16 (36%) as negative regarding activities. Patients that reported AWA were younger and had a higher body mass index at surgery (P = 0.03 and 0.04, respectively).Conclusion: Abdominal wall asymmetry is a common sequel of flank incision for OPN and is associated with a higher incidence of chronic pain and abdominal stiffness compared to absence of postoperative AWA. Some patients reported that the effect on daily activities and the cosmetic effect caused by AWA had a negative impact on their quality of life.
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| 10. |
- Lambregts, Doenja M. J., et al.
(author)
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Current controversies in TNM for the radiological staging of rectal cancer and how to deal with them : results of a global online survey and multidisciplinary expert consensus
- 2022
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In: European Radiology. - : Springer Nature. - 0938-7994 .- 1432-1084. ; 32:7, s. 4991-5003
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Journal article (peer-reviewed)abstract
- Objectives To identify the main problem areas in the applicability of the current TNM staging system (8(th) ed.) for the radiological staging and reporting of rectal cancer and provide practice recommendations on how to handle them. Methods A global case-based online survey was conducted including 41 image-based rectal cancer cases focusing on various items included in the TNM system. Cases reaching < 80% agreement among survey respondents were identified as problem areas and discussed among an international expert panel, including 5 radiologists, 6 colorectal surgeons, 4 radiation oncologists, and 3 pathologists. Results Three hundred twenty-one respondents (from 32 countries) completed the survey. Sixteen problem areas were identified, related to cT staging in low-rectal cancers, definitions for cT4b and cM1a disease, definitions for mesorectal fascia (MRF) involvement, evaluation of lymph nodes versus tumor deposits, and staging of lateral lymph nodes. The expert panel recommended strategies on how to handle these, including advice on cT-stage categorization in case of involvement of different layers of the anal canal, specifications on which structures to include in the definition of cT4b disease, how to define MRF involvement by the primary tumor and other tumor-bearing structures, how to differentiate and report lymph nodes and tumor deposits on MRI, and how to anatomically localize and stage lateral lymph nodes. Conclusions The recommendations derived from this global survey and expert panel discussion may serve as a practice guide and support tool for radiologists (and other clinicians) involved in the staging of rectal cancer and may contribute to improved consistency in radiological staging and reporting.
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