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| 2. |
- de Boniface, J., et al.
(författare)
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Omitting axillary dissection in breast cancer with sentinel-node metastases
- 2024
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 390:13, s. 1163-1175
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Trials evaluating the omission of completion axillary-lymph-node dissection in patients with clinically node-negative breast cancer and sentinel-lymph-node metastases have been compromised by limited statistical power, uncertain nodal radiotherapy target volumes, and a scarcity of data on relevant clinical subgroups.METHODS We conducted a noninferiority trial in which patients with clinically node-negative primary T1 to T3 breast cancer (tumor size, T1, ≤20 mm; T2, 21 to 50 mm; and T3, >50 mm in the largest dimension) with one or two sentinel-node macrometastases (metastasis size, >2 mm in the largest dimension) were randomly assigned in a 1:1 ratio to completion axillary-lymph-node dissection or its omission (sentinel-node biopsy only). Adjuvant treatment and radiation therapy were used in accordance with national guidelines. The primary end point was overall survival. We report here the per-protocol and modified intention-to-treat analyses of the prespecified secondary end point of recurrence-free survival. To show noninferiority of sentinel-node biopsy only, the upper boundary of the confidence interval for the hazard ratio for recurrence or death had to be below 1.44.RESULTS Between January 2015 and December 2021, a total of 2766 patients were enrolled across five countries. The per-protocol population included 2540 patients, of whom 1335 were assigned to undergo sentinel-node biopsy only and 1205 to undergo completion axillary-lymph-node dissection (dissection group). Radiation therapy including nodal target volumes was administered to 1192 of 1326 patients (89.9%) in the sentinel-node biopsy–only group and to 1058 of 1197 (88.4%) in the dissection group. The median follow-up was 46.8 months (range, 1.5 to 94.5). Overall, 191 patients had recurrence or died. The estimated 5-year recurrence-free survival was 89.7% (95% confidence interval [CI], 87.5 to 91.9) in the sentinel-node biopsy–only group and 88.7% (95% CI, 86.3 to 91.1) in the dissection group, with a country-adjusted hazard ratio for recurrence or death of 0.89 (95% CI, 0.66 to 1.19), which was significantly (P<0.001) below the prespecified noninferiority margin.CONCLUSIONS The omission of completion axillary-lymph-node dissection was noninferior to the more extensive surgery in patients with clinically node-negative breast cancer who had sentinel-node macrometastases, most of whom received nodal radiation therapy. (Funded by the Swedish Research Council and others; SENOMAC ClinicalTrials.gov number, NCT02240472.).
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| 3. |
- Ercan, Ayse Bahar, et al.
(författare)
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Clinical and biological landscape of constitutional mismatch-repair deficiency syndrome: an International Replication Repair Deficiency Consortium cohort study.
- 2024
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Ingår i: The Lancet. Oncology. - 1474-5488. ; 25:5, s. 668-682
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Tidskriftsartikel (refereegranskat)abstract
- Constitutional mismatch repair deficiency (CMMRD) syndrome is a rare and aggressive cancer predisposition syndrome. Because a scarcity of data on this condition contributes to management challenges and poor outcomes, we aimed to describe the clinical spectrum, cancer biology, and impact of genetics on patient survival in CMMRD.In this cohort study, we collected cross-sectional and longitudinal data on all patients with CMMRD, with no age limits, registered with the International Replication Repair Deficiency Consortium (IRRDC) across more than 50 countries. Clinical data were extracted from the IRRDC database, medical records, and physician-completed case record forms. The primary objective was to describe the clinical features, cancer spectrum, and biology of the condition. Secondary objectives included estimations of cancer incidence and of the impact of the specific mismatch-repair gene and genotype on cancer onset and survival, including after cancer surveillance and immunotherapy interventions.We analysed data from 201 patients (103 males, 98 females) enrolled between June 5, 2007 and Sept 9, 2022. Median age at diagnosis of CMMRD or a related cancer was 8·9 years (IQR 5·9-12·6), and median follow-up from diagnosis was 7·2 years (3·6-14·8). Endogamy among minorities and closed communities contributed to high homozygosity within countries with low consanguinity. Frequent dermatological manifestations (117 [93%] of 126 patients with complete data) led to a clinical overlap with neurofibromatosis type 1 (35 [28%] of 126). 339 cancers were reported in 194 (97%) of 201 patients. The cumulative cancer incidence by age 18 years was 90% (95% CI 80-99). Median time between cancer diagnoses for patients with more than one cancer was 1·9 years (IQR 0·8-3·9). Neoplasms developed in 15 organs and included early-onset adult cancers. CNS tumours were the most frequent (173 [51%] cancers), followed by gastrointestinal (75 [22%]), haematological (61 [18%]), and other cancer types (30 [9%]). Patients with CNS tumours had the poorest overall survival rates (39% [95% CI 30-52] at 10 years from diagnosis; log-rank p<0·0001 across four cancer types), followed by those with haematological cancers (67% [55-82]), gastrointestinal cancers (89% [81-97]), and other solid tumours (96% [88-100]). All cancers showed high mutation and microsatellite indel burdens, and pathognomonic mutational signatures. MLH1 or MSH2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall survival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0% for MSH2; p<0·0001). Frameshift or truncating variants within the same gene caused earlier cancers and inferior outcomes compared with missense variants (p<0·0001). The greater deleterious effects of MLH1 and MSH2 variants as compared with PMS2 and MSH6 variants persisted despite overall improvements in survival after surveillance or immune checkpoint inhibitor interventions.The very high cancer burden and unique genomic landscape of CMMRD highlight the benefit of comprehensive assays in timely diagnosis and precision approaches toward surveillance and immunotherapy. These data will guide the clinical management of children and patients who survive into adulthood with CMMRD.The Canadian Institutes for Health Research, Stand Up to Cancer, Children's Oncology Group National Cancer Institute Community Oncology Research Program, Canadian Cancer Society, Brain Canada, The V Foundation for Cancer Research, BioCanRx, Harry and Agnieszka Hall, Meagan's Walk, BRAINchild Canada, The LivWise Foundation, St Baldrick Foundation, Hold'em for Life, and Garron Family Cancer Center.
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| 5. |
- Andernord, D., et al.
(författare)
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Contact allergy to haptens in the Swedish baseline series: Results from the Swedish Patch Test Register (2010 to 2017)
- 2022
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 86:3, s. 175-188
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Tidskriftsartikel (refereegranskat)abstract
- Background Allergic contact dermatitis has considerable public health impact and causative haptens vary over time. Objectives To report the prevalence of contact allergy to allergens in the Swedish baseline series 2010 to 2017, as registered in the Swedish Patch Test Register. Methods Results and demographic information for patients tested with the Swedish baseline series in 2010 to 2017 were analysed. Results Data for 21 663 individuals (females 69%) were included. Females had significantly more positive patch tests (54% vs 40%). The reaction prevalence rates were highest for nickel sulfate (20.7%), fragrance mix I (7.1%), Myroxylon pereirae (6.9%), potassium dichromate (6.9%), cobalt chloride (6.8%), methylchloroisothiazolinone/methylisothiazolinone (MCI/MI; 6.4%), MI (3.7%), colophonium (3.5%), fragrance mix II (3.2%), and formaldehyde (3.2%). Myroxylon pereirae reaction prevalence increased from 5% in 2010 to 9% in 2017 and that for methyldibromo glutaronitrile from 3.1% to 4.6%. MCI/MI and MI reactions decreased in prevalence after 2014. Nickel reaction prevalence decreased among females aged 10 to 19 years. Conclusions Nickel remains the most common sensitizing agent, with reaction prevalence decreasing among females younger than 20 years. The changes in MCI/MI and MI reaction prevalence mirrored those in Europe. The register can reveal changes in contact allergy prevalence over time among patients patch tested in Sweden.
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| 6. |
- Anker, I., et al.
(författare)
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Luxation du nerf ulnaire lors du syndrome canalaire au coude. Influence sur le résultat chirurgical
- 2022
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Ingår i: Hand Surgery and Rehabilitation. - : Elsevier BV. - 2468-1229. ; 41:1, s. 96-102
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Tidskriftsartikel (refereegranskat)abstract
- Our aim was to assess the incidence of symptomatic ulnar nerve dislocation and its influence on surgical outcome after primary and revision surgeries in ulnar nerve entrapment at the elbow (ulnar neuropathy at the elbow (UNE) or cubital tunnel syndrome). The influence of pre- or intra-operative ulnar nerve dislocation on postoperative outcome was assessed in 548 surgically treated cases (548 nerves) from two hand surgery departments reporting to the Swedish National Quality Registry for Hand Surgery, using QuickDASH, a patient-reported outcome measure (PROM), before surgery and at 3 and 12 months postoperatively, and a doctor-reported outcome measure (DROM), grading as “cured-improved “or “unchanged-worsened,” at a median follow-up of 3.0 months [IQR, 1.5–6.0]. 109 of the 548 cases (20%) showed documented pre- or intra-operative ulnar nerve dislocation; more often found at revision (35/75, 47%) than at primary surgery (74/473, 16%) (p < 0.0001). Cases with dislocation presented higher QuickDASH scores at 12 months (p = 0.026). A linear regression model, adjusted for age and gender, predicted higher QuickDASH scores at 12 months postoperatively for cases with dislocation (unstandardized B 11.3 [95% CI 0.4–22.2], p = 0.043). DROM grading as unchanged-worsened at a median 3 months predicted worse QuickDASH scores (p < 0.0001) than in cured-improved cases at 3 (unstandardized B, 18.4 [95% CI 9.4–27.3]) and 12 months (unstandardized B, 18.1 [9.1–27.0]). Primary surgeries had better DROM grading than revision surgeries (p = 0.033; cured-improved, 75% and 63%, respectively), but QuickDASH scores did not differ. Presence of a clinically relevant ulnar nerve dislocation resulted in worse outcome, perhaps due to more extensive surgery with transposition. Nerve dislocation needs attention when treating UNE patients.
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| 7. |
- Axelsson, Lars, et al.
(författare)
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Swedish National Multicenter Study on Head and Neck Cancer of Unknown Primary: Prognostic Factors and Impact of Treatment on Survival
- 2021
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Ingår i: International Archives of Otorhinolaryngology. - : Georg Thieme Verlag KG. - 1809-9777 .- 1809-4864. ; 25:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Head and neck cancer of unknown primary (HNCUP) is a rare condition whose prognostic factors that are significant for survival vary between studies. No randomized treatment study has been performed thus far, and the optimal treatment is not established. Objective The present study aimed to explore various prognostic factors and compare the two main treatments for HNCUP: neck dissection and (chemo) radiation vs primary (chemo) radiation. Methods A national multicenter study was performed with data from the Swedish Head and Neck Cancer Register (SweHNCR) and from the patients' medical records from 2008 to 2012. Results Two-hundred and sixty HNCUP patients were included. The tumors were HPVpositive in 80%. The overall 5-year survival rate of patients treated with curative intent was 71%. Age (p < 0.001), performance status (p = 0.036), and N stage (p = 0.046) were significant factors for overall survival according to the multivariable analysis. Treatment with neck dissection and (chemo) radiation (122 patients) gave an overall 5-year survival of 73%, and treatment with primary (chemo) radiation (87 patients) gave an overall 5-year survival of 71%, with no significant difference in overall or disease-free survival between the 2 groups. Conclusions Age, performance status, and N stage were significant prognostic factors. Treatment with neck dissection and ( chemo) radiation and primary (chemo)
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| 8. |
- Ben Chouikha, I., et al.
(författare)
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Quantum chemical study of the reaction paths and kinetics of acetaldehyde formation on a methanol-water ice model
- 2022
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Ingår i: RSC Advances. - : Royal Society of Chemistry (RSC). - 2046-2069. ; 12:29, s. 18994-19005
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Tidskriftsartikel (refereegranskat)abstract
- Acetaldehyde (CH3CHO) is ubiquitous in interstellar space and is important for astrochemistry as it can contribute to the formation of amino acids through reaction with nitrogen containing chemical species. Quantum chemical and reaction kinetics studies are reported for acetaldehyde formation from the chemical reaction of C(P-3) with a methanol molecule adsorbed at the eighth position of a cubic water cluster. We present extensive quantum chemical calculations for total spin S = 1 and S = 0. The U omega B97XD/6-311++G(2d,p) model chemistry is employed to optimize the structures, compute minimum energy paths and zero-point vibrational energies of all reaction steps. For the optimized structures, the calculated energies are refined by CCSD(T) single point computations. We identify four transition states on the triplet potential energy surface (PES), and one on the singlet PES. The reaction mechanism involves the intermediate formation of CH3OCH adsorbed on the ice cluster. The rate limiting step for forming acetaldehyde is the C-O bond breaking in CH3OCH to form adsorbed CH3 and HCO. We find two positions on the reaction path where spin crossing may be possible such that acetaldehyde can form in its singlet spin state. Using variational transition-state theory with multidimensional tunnelling we provide thermal rate constants for the energetically rate limiting step for both spin states and discuss two routes to acetaldehyde formation. As expected, quantum effects are important at low temperatures.
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| 9. |
- Berg, Malin, 1976, et al.
(författare)
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Fatigue in Long-Term Head and Neck Cancer Survivors From Diagnosis Until Five Years After Treatment
- 2023
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Ingår i: Laryngoscope. - : Wiley. - 0023-852X.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Fatigue due to cancer is a challenging symptom that might be long-lasting after cancer treatment. The aim of this study was to follow the development of fatigue among head and neck cancer (HNC) patients prospectively and longitudinally and to analyze predictors for acute and chronic fatigue. Methods: HNC patients treated with curative intent were included at diagnosis and completed the following questionnaires multiple times, up to 5 years after treatment: the EORTC QLQ-FA12 for fatigue, EORTC QLQ-C30, and HNC-specific EORTC QLQ-H&N35 together with an anxiety and depression questionnaire. Predictors of fatigue were evaluated at 3 months and 5 years after treatment. Results: Of the 311 study participants, 74% responded at the 5-year follow-up. Physical fatigue was significantly worse 3 months after treatment, while emotional and cognitive fatigue were the worst at diagnosis and at 3 months. All fatigue domains were significantly better after 1 year, and the fatigue scores remained stable from 1 until 5 years after treatment. Three months after chemoradiotherapy, physical fatigue was more significant, but no long-term differences due to treatment modalities were found. Depression and anxiety were predictors for chronic emotional fatigue, and local HN pain and swallowing problems were predictors for chronic physical fatigue. Better global quality of life at diagnosis was associated with less physical and emotional fatigue. Conclusion: Fatigue was worst in the short term for HNC patients and improved after 1 year, and long-term fatigue remained stable up to 5 years after treatment. A few predictors for chronic fatigue were found. Level of Evidence: 3 Laryngoscope, 2023. © 2023 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.
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| 10. |
- Berg, Malin, 1976, et al.
(författare)
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The effect of age on health-related quality of life for head and neck cancer patients up to 1 year after curative treatment
- 2022
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Ingår i: Journal of Geriatric Oncology. - : Elsevier BV. - 1879-4068. ; 13:1, s. 60-66
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim was to evaluate the effect of age on health-related quality of life (HRQOL) for patients with head and neck cancer (HNC), treated with curative intent, in the Western healthcare region of Sweden. Materials and Methods: In this prospective observational study, 311 HNC patients completed quality of life questionnaires for cancer (EORTC QLQ-C30 and EORTC QLQ-H&N35) and for older patients with cancer (EORT QLQELD14) at diagnosis and 3, 6, and 12 months after start of treatment. Mean scores for patients >_70 years old were compared to younger patients (50 to 69 years old) to assess differences in HRQOL. Results: Of the 311 study participants, 105 patients were >_70 years old (median age 76.7), of which 32 were >_80 years of age. Most HRQOL scores were equal or better for older adult patients at 3 months after treatment, but physical function was better for younger adult patients up to 12 months after treatment. At 6 months the HRQOL was similar (older patients had less appetite loss and financial difficulties), while the oldest patients (>_80 years) had worse fatigue, role function, and feeling ill at 12 months. For the EORTC-ELD-14 questionnaire, older patients scored better for worries at diagnosis and reported more difficulties in maintaining purpose at 12 months after treatment. Conclusion: When curative treatment is administered, older adult patients with HNC have similar or even better HRQOL compared to younger adult patients, except for physical function, during the first year. (c) 2021 Elsevier Ltd. All rights reserved.
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