Publications by authors named "Kjersti Hornslien"

9 Publications

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High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial.

Lancet Oncol 2021 03;22(3):321-331

Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.

Background: Concurrent chemoradiotherapy is standard treatment for limited stage small-cell lung cancer (SCLC). Twice-daily thoracic radiotherapy of 45 Gy in 30 fractions is considered to be the most effective schedule. The aim of this study was to investigate whether high-dose, twice-daily thoracic radiotherapy of 60 Gy in 40 fractions improves survival.

Methods: This open-label, randomised, phase 2 trial was done at 22 public hospitals in Norway, Denmark, and Sweden. Patients aged 18 years and older with treatment-naive confirmed limited stage SCLC, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, and measurable disease according to the Response Evaluation Criteria in Solid Tumors version 1.1 were eligible. All participants received four courses of intravenous cisplatin 75 mg/m or carboplatin (area under the curve 5-6 mg/mL × min, Calvert's formula) on day 1 and intravenous etoposide 100 mg/m on days 1-3 every 3 weeks. Participants were randomly assigned (1:1) in permuted blocks (sized between 4 and 10) stratifying for ECOG performance status, disease stage, and presence of pleural effusion to receive thoracic radiotherapy of 45 Gy in 30 fractions or 60 Gy in 40 fractions to the primary lung tumour and PET-CT positive lymph node metastases starting 20-28 days after the first chemotherapy course. Patients in both groups received two fractions per day, ten fractions per week. Responders were offered prophylactic cranial irradiation of 25-30 Gy. The primary endpoint, 2-year overall survival, was assessed after all patients had been followed up for a minimum of 2 years. All randomly assigned patients were included in the efficacy analyses, patients commencing thoracic radiotherapy were included in the safety analyses. Follow-up is ongoing. This trial is registered at ClinicalTrials.gov, NCT02041845.

Findings: Between July 8, 2014, and June 6, 2018, 176 patients were enrolled, 170 of whom were randomly assigned to 60 Gy (n=89) or 45 Gy (n=81). Median follow-up for the primary analysis was 49 months (IQR 38-56). At 2 years, 66 (74·2% [95% CI 63·8-82·9]) patients in the 60 Gy group were alive, compared with 39 (48·1% [36·9-59·5]) patients in the 45 Gy group (odds ratio 3·09 [95% CI 1·62-5·89]; p=0·0005). The most common grade 3-4 adverse events were neutropenia (72 [81%] of 89 patients in the 60 Gy group vs 62 [81%] of 77 patients in the 45 Gy group), neutropenic infections (24 [27%] vs 30 [39%]), thrombocytopenia (21 [24%] vs 19 [25%]), anaemia (14 [16%] vs 15 [20%]), and oesophagitis (19 [21%] vs 14 [18%]). There were 55 serious adverse events in 38 patients in the 60 Gy group and 56 serious adverse events in 44 patients in the 45 Gy group. There were three treatment-related deaths in each group (one neutropenic fever, one aortic dissection, and one pneumonitis in the 60 Gy group; one thrombocytic bleeding, one cerebral infarction, and one myocardial infarction in the 45 Gy group).

Interpretation: The higher radiotherapy dose of 60 Gy resulted in a substantial survival improvement compared with 45 Gy, without increased toxicity, suggesting that twice-daily thoracic radiotherapy of 60 Gy is an alternative to existing schedules.

Funding: The Norwegian Cancer Society, The Liaison Committee for Education, Research and Innovation in Central Norway, the Nordic Cancer Union, and the Norwegian University of Science and Technology.
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http://dx.doi.org/10.1016/S1470-2045(20)30742-7DOI Listing
March 2021

Gender effects on quality of life and symptom burden in patients with lung cancer: results from a prospective, cross-cultural, multi-center study.

J Thorac Dis 2020 Aug;12(8):4253-4261

Center for Clinical Studies, University Hospital Regensburg, Regensburg, Germany.

Background: Lung cancer causes impairment of health-related quality of life (QoL), but little is known about gender aspects in QoL and symptom burden of lung cancer patients. The aim of this study was to investigate gender differences in QoL as assessed by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the updated lung cancer module.

Methods: In a prospective, international, cross-cultural, multicenter study that was undertaken to update the lung cancer-specific module EORTC QLQ-LC13, patients filled in the core questionnaire EORTC QLQ-C30 and the updated lung cancer module. Gender differences were calculated for all QoL scores using ANCOVAs that controlled for known and suspected confounders. Comparisons with historic data were drawn.

Results: A total of 200 patients (82 female and 118 male, median age 65 years) were recruited. With the exception of coughing (estimated marginal means: women 33.86 and men 43.52, P=0.022) and diarrhea (estimated marginal means: women 26.01 and men 17.93, P=0.038) there were no significant QoL gender differences. Fatigue was the most pronounced symptom in both, men and women, outpacing typical respiratory symptoms. Quite generally, our sample of lung cancer patients showed considerably worse QoL in all scores when compared to EORTC reference data (lung cancer and combined cancer diagnoses, mean differences up to 13.70 and 21.54 score points, respectively) and to a German norm reference sample (up to 35.37 score points).

Conclusions: This study adds to the literature in showing that the typical QoL gender difference effect (women doing worse than men) may not be generalizable across all patient samples.
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http://dx.doi.org/10.21037/jtd-20-1054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7475557PMC
August 2020

Randomized phase III trial comparing switch-maintenance pemetrexed with observation followed by pemetrexed at progression in advanced NSCLC.

Acta Oncol 2020 Sep 16;59(9):1051-1057. Epub 2020 Jun 16.

Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway.

Two phase III trials show that maintenance pemetrexed therapy after platinum-doublet chemotherapy prolongs overall survival (OS) and progression free survival (PFS) in advanced non-squamous non-small-cell lung cancer (NSCLC). However, few patients in the control arms received pemetrexed at progression in these trials, performance status (PS) two patients were ineligible and few of the participants were elderly. Thus, we designed this study comparing immediate switchmaintenance pemetrexed therapy with pemetrexed at progression after platinum-doublet chemotherapy. Patients with stage IIIB/IV non-squamous NSCLC, ≥18 years, PS 0-2, and non-progression after four courses of carboplatin/vinorelbine were randomized to receive immediate maintenance pemetrexed therapy or observation followed by pemetrexed at progression. The primary endpoint was OS, secondary endpoints were PFS, toxicity and health related quality of life (HRQoL). 105 patients were randomized between May 2014 and September 2017. Median age was 67 years, 36% were >70 years, 9% had PS 2, 91% stage IV and 47% were women. In the observation arm, 73% received pemetrexed at progression. Patients in the maintenance arm had a numerically longer OS (median 12.0 vs. 10.0 months;  = .10) and a statistically significant longer PFS (median 3.1 vs. 1.9 months;  < .01). In multivariable analyses adjusting for baseline characteristics, there was a trend toward improved OS (HR 0.65, 95% CI 0.42-1.01);  = .05), and a significantly improved PFS (HR 0.53, 95% CI 0.35-0.80;  < .01). There were no significant differences in toxicity or HRQoL between the treatment arms. There was a trend toward prolonged OS and significantly longer PFS from switch maintenance pemetrexed therapy when 73% of patients in the control arm received pemetrexed at progression. NCT02004184.
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http://dx.doi.org/10.1080/0284186X.2020.1778179DOI Listing
September 2020

Psychometric properties of the updated EORTC module for assessing quality of life in patients with lung cancer (QLQ-LC29): an international, observational field study.

Lancet Oncol 2020 05 23;21(5):723-732. Epub 2020 Mar 23.

Quality of Life Department, European Organisation for Research and Treatment of Cancer, Brussels, Belgium.

Background: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13) assesses quality of life (QOL) in patients with lung cancer and was the first EORTC module developed for use in international clinical trials. Since its publication in 1994, major treatment advances with possible effects on QOL have occurred. These changes called for an update of the module and its international psychometric validation. We aimed to investigate the scale structure and psychometric properties of the updated lung cancer module, QLQ-LC29, in patients with lung cancer.

Methods: This international, observational field study was done in 19 hospitals across 12 countries. Patients aged older than 18 years with a confirmed diagnosis of lung cancer and no other previous primary tumour, and who were mentally fit with sufficient language skills to understand and complete the questionnaire were included. Patients were asked during a hospital visit to fill in the paper versions of the core questionnaire EORTC QLQ-C30 plus QLQ-LC29, and investigators selected half of these patients to complete the questionnaire again 2-4 weeks later. Our primary aim was to assess the scale structure and psychometric properties of EORTC QLQ-LC29. We analysed scale structure using confirmatory factor analysis; reliability using Cronbach's α value (internal consistency) and intra-class coefficient (test-retest reliability); sensitivity using independent t tests stratified by Karnofsky performance status; and responsiveness to change over time by ANOVA. This study is registered with ClinicalTrials.gov, NCT02745691.

Findings: Between April 12, 2016, and Sept 26, 2018, 523 patients with a confirmed diagnosis of either non-small-cell lung cancer (n=442) or small-cell lung cancer (n=81) were recruited. Confirmatory factor analysis provided a solution composed of five multi-item scales (coughing, shortness of breath, fear of progression, hair problems, and surgery-related symptoms) plus 15 single symptom or side-effect items: χ=370·233, root mean square error of approximation=0·075, and comparative-fit index=0·901. Cronbach's α for internal consistencies of all multi-item scales were above the threshold of 0·70. Intra-class coefficients for test-retest reliabilities ranged between 0·82 and 0·97. Three (shortness of breath, fear of progression, and hair problems) of the five multi-item scales showed responsiveness to change over time (p values <0·05), as did nine of 15 single symptom items. Four (coughing, shortness of breath, fear of progression, and surgery-related symptoms) of the five multi-item scales and ten of the 15 single symptom items were sensitive to known group differences (ie, lower vs higher Karnofsky performance status).

Interpretation: Results determined the psychometric properties of the updated lung cancer module, which is ready for use in international clinical studies.

Funding: EORTC Quality of Life Group.
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http://dx.doi.org/10.1016/S1470-2045(20)30093-0DOI Listing
May 2020

Randomized phase II trial comparing twice daily hyperfractionated with once daily hypofractionated thoracic radiotherapy in limited disease small cell lung cancer.

Acta Oncol 2016 May 23;55(5):591-7. Epub 2015 Oct 23.

b Clinic of Oncology, St. Olavs Hospital, Trondheim University Hospital , Trondheim , Norway .

Background: Concurrent chemotherapy and thoracic radiotherapy (TRT) is recommended for limited disease small cell lung cancer (LD SCLC). Twice daily TRT is well documented, but not universally implemented - probably mainly due to inconvenience and concerns about toxicity. A schedule of three-week hypofractionated TRT is a commonly used alternative. This is the first randomized trial comparing twice daily and hypofractionated TRT in LD SCLC.

Material And Methods: Patients received four courses of cisplatin/etoposide (PE) and were randomized to TRT of 42 Gy in 15 fractions (once daily, OD) or 45 Gy in 30 fractions (twice daily, BID) between the second and third PE course. Good responders received prophylactic cranial irradiation of 30 Gy in 15 fractions.

Results: 157 patients were enrolled between May 2005 and January 2011 (OD: n = 84, BID: n = 73). Median age was 63 years, 52% were men, 84% had performance status 0-1, 72% had stage III disease and 11% non-malignant pleural effusion. The treatment arms were well balanced. The response rates were similar (OD: 92%, BID: 88%; p = 0.41), but more BID patients achieved a complete response (OD: 13%, BID: 33%; p = 0.003). There was no difference in one-year progression-free survival (PFS) (OD: 45%, BID: 49%; p = 0.61) or median PFS (OD: 10.2 months, BID: 11.4 months; p = 0.93). The median overall survival in the BID arm was 6.3 months longer (OD: 18.8 months, BID: 25.1 months; p = 0.61). There were no differences in grade 3-4 esophagitis (OD: 31%, BID: 33%, p = 0.80) or pneumonitis (OD: 2%, BID: 3%, p = 1.0). Patients on the BID arm reported slightly more dysphagia at the end of the TRT.

Conclusion: There was no difference in severe toxicity between the two TRT schedules. The twice daily schedule resulted in significantly more complete responses and a numerically longer median overall survival, but no firm conclusions about efficacy could be drawn from this phase II trial.
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http://dx.doi.org/10.3109/0284186X.2015.1092584DOI Listing
May 2016

Potentially curative radiotherapy for non-small-cell lung cancer in Norway: a population-based study of survival.

Int J Radiat Oncol Biol Phys 2011 May 6;80(1):133-41. Epub 2010 May 6.

Department of Clinical and Registry-based Research, Cancer Registry of Norway, Oslo, Norway.

Purpose: The efficacy of curative irradiation in the treatment of non-small-cell lung cancer patients is considered limited. The purpose of this study was to evaluate long-term survival in a population-based approach.

Methods And Materials: Cases of non-small-cell lung cancer diagnosed from 1993 to 2001 were identified in the Cancer Registry of Norway. Electronic linkage with national data from the hospitals' radiotherapy verification systems identified those who received potentially curative doses (≥ 50 Gy). Hospital records were reviewed for all patients.

Results: A total of 497 patients (336 men) were identified with a radiation dose of ≥ 50 Gy delivered to the lung region. Of these, 41% received 60 Gy or more. The majority (70%) of patients included had advanced stage disease: 24% Stage IIIA and 46% Stage IIIB. The overall 1-, 3-, and 5-year observed survival rates were 53%, 16%, and 9%, respectively. Multivariable analyses identified stage and chemotherapy, but not radiation dose, as significant independent prognostic variables for survival. However, 68% of patients treated with chemotherapy participated in prospective studies with inclusion criteria that excluded patients with less favorable prognostic factors, leading to a selection bias. The number of fractions and the radiation doses varied widely among different hospitals.

Conclusion: The long-term prognosis after radiation therapy is poor. More sophisticated, targeted, and uniform delivery of radiation therapy is needed. The apparent benefit of chemotherapy may in part be due to selection of patients with more favorable prognostic factors for this therapy.
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http://dx.doi.org/10.1016/j.ijrobp.2010.01.050DOI Listing
May 2011

Long-term follow-up of cancer patients receiving radiotherapy for bone metastases: results from a randomised multicentre trial.

Radiother Oncol 2009 May 21;91(2):261-6. Epub 2009 Mar 21.

Faculty of Medicine, Norwegian University of Technology and Science, Trondheim, Norway.

Background And Purpose: The aim of this study was to compare the need for re-irradiation, rates of pathological fractures, and spinal cord compressions in patients randomised to single-fraction radiotherapy (8 Gy x 1) or multiple-fraction therapy (3 Gy x 10) and with a long-term follow-up. The underlying hypothesis was that single-fraction and multiple-fraction regimens are equally effective.

Material And Methods: The present study reports on the Norwegian sub sample of an international large prospective-randomised multicentre study. One hundred and eighty patients with painful skeletal metastases in four Norwegian hospitals were randomised to receive single-fraction (8 Gy x 1) or multiple-fraction (3 Gy x 10) radiotherapy.

Results: Patients in the single-fraction arm received significantly more re-irradiations as compared to the multiple-fraction arm (27% versus 9%, p=0.002). There were no significant differences in the rate of pathological fractures (5% versus 5%, p=1.00) or spinal cord compressions (1% versus 4%, p=0.37) between the two treatment groups.

Conclusion: The present study indicates no difference between radiotherapy with 8 Gy x 1 and 3 Gy x 10 for the majority of patients with painful bone metastases, also in a long-term perspective. Importantly, the patients in this study were followed up until death, and the trial showed no disadvantage for 8 Gy x 1 compared to 3 Gy x 10. Despite the fact that single-fraction treatment will imply an approximately 2.5-fold greater need for re-irradiation, single-fraction treatment is considered more convenient for the patients and more cost-effective for the radiotherapy departments.
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http://dx.doi.org/10.1016/j.radonc.2009.02.014DOI Listing
May 2009

Effectiveness of physical activity on cardiorespiratory fitness and health-related quality of life in young and middle-aged cancer patients shortly after chemotherapy.

J Clin Oncol 2005 Apr;23(10):2378-88

Department of Psychosocial Oncology and Rehabilitation, The Norwegian Radium Hospital, N-0310 Oslo, Norway.

Purpose: To evaluate the effectiveness of a supervised home-based flexible training program on cardiorespiratory fitness (CRF), mental distress, and health-related quality of life (HRQOL) parameters in young and middle-aged cancer patients shortly after curative chemotherapy.

Patients And Methods: One hundred eleven patients age 18 to 50 years who had received chemotherapy for lymphomas or breast, gynecologic, or testicular cancer completed the trial. These patients were randomly allocated to either an intervention group (n = 59), which underwent a 14-week training program, or a control group (n = 52) that received standard care. Primary outcome was change in CRF, as determined by Astrand-Rhyming indirect bicycle ergometer test (maximum oxygen uptake [VO(2max)]), between baseline (T0) and follow-up (T1). Secondary outcomes were mental distress, as assessed by the Hospital Anxiety and Depression Scale, and HRQOL, as assessed by the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire. Two-way analysis of covariance was used to analyze changes from T0 to T1.

Results: VO(2max) increased by 6.4 mL/kg(-1)/min(-1) in patients in the intervention group and by 3.1 mL/kg(-1)/min(-1) in patients in the control group (P < .01). The fatigue score decreased by 17.0 points in the control group compared with only 5.8 points in the intervention group (P < .01). There were no intergroup differences in mental distress or HRQOL.

Conclusion: A supervised, home-based, flexible training program has significant effect on CRF in young and middle-aged cancer patients shortly after curative chemotherapy, but it has no favorable effect on patients' experience of fatigue, mental distress, or HRQOL.
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http://dx.doi.org/10.1200/JCO.2005.04.106DOI Listing
April 2005