Publications by authors named "Carsten Nieder"

285 Publications

Primary systemic therapy for patients with brain metastases from lung cancer ineligible for targeted agents.

J Cancer Res Clin Oncol 2022 Jan 12. Epub 2022 Jan 12.

Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway.

Purpose: The purpose of this study was to evaluate overall survival after systemic therapy, largely chemotherapy, in patients with small cell or non-small cell lung cancer and brain metastases. After completion of systemic therapy, some patients received planned brain irradiation, while others were followed.

Methods: Retrospective cohort study.

Results: Thirty-eight patients were included (28 small cell, 20 followed with imaging). Six of these 20 patients (30%) received delayed radiotherapy during follow-up. Planned radiotherapy (n = 18, intention-to-treat) was associated with longer survival from diagnosis of brain metastases, median 10.8 versus 6.1 months, p = 0.025. Delayed radiotherapy still resulted in numerically better survival than no radiotherapy at all (median 8.8 versus 5.3 months, not significant). If calculated from the start of delayed radiotherapy, median survival was only 2.7 months. In a multivariable analysis, both Karnofsky performance status ≥ 70 (p = 0.03) and planned radiotherapy (p = 0.05) were associated with better survival.

Conclusion: In patients ineligible for targeted agents, planned radiotherapy in a modern treatment setting was associated with longer survival compared to no radiotherapy. Timing and type of radiotherapy in such patients should be evaluated in prospective trials to identify patients who might not need planned radiotherapy.
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http://dx.doi.org/10.1007/s00432-022-03919-0DOI Listing
January 2022

The LabBM score is an excellent survival prediction tool in patients undergoing palliative radiotherapy.

Rep Pract Oncol Radiother 2021 30;26(5):740-746. Epub 2021 Sep 30.

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Background And Aim: The prognostic assessment of patients referred for palliative radiotherapy can be conducted by site-specific scores. A quick assessment that would cover the whole spectrum could simplify the working day of clinicians who are not specialists for a particular disease site. This study evaluated a promising score, the LabBM (validated for brain metastases), in patients treated for other indications.

Materials And Methods: The LabBM score was calculated in 375 patients by assigning 1 point each for C-reactive protein and lactate dehydrogenase above the upper limit of normal, and 0.5 points each for hemoglobin, platelets and albumin below the lower limit of normal. Uni- and multivariate analyses were performed.

Results: Median overall survival gradually decreased with increasing point sum (range 25.1-1.1 months). When grouped according to the original three-tiered model, excellent discrimination was found. Patients with 0-1 points had a median survival of 15.7 months. Those with 1.5-2 points had a median survival of 5.8 months. Finally, those with 2.5-3.5 points had a median survival of 3.2 months (all p-values ≤ 0.001).

Conclusion: The LabBM score, which is derived from inexpensive blood tests and easy to use, stratified patients into three very distinct prognostic groups and deserves further validation.
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http://dx.doi.org/10.5603/RPOR.a2021.0096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575363PMC
September 2021

Hippocampus-Avoidance Whole-Brain Radiation Therapy Is Efficient in the Long-Term Preservation of Hippocampal Volume.

Front Oncol 2021 19;11:714709. Epub 2021 Aug 19.

Department of Neuroradiology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background And Purpose: With improved life expectancy, preventing neurocognitive decline after cerebral radiotherapy is gaining more importance. Hippocampal damage has been considered the main culprit for cognitive deficits following conventional whole-brain radiation therapy (WBRT). Here, we aimed to determine to which extent hippocampus-avoidance WBRT (HA-WBRT) can prevent hippocampal atrophy compared to conventional WBRT.

Methods And Materials: Thirty-five HA-WBRT and 48 WBRT patients were retrospectively selected, comprising a total of 544 contrast-enhanced T1-weighted magnetic resonance imaging studies, longitudinally acquired within 24 months before and 48 months after radiotherapy. HA-WBRT patients were treated analogously to the ongoing HIPPORAD-trial (DRKS00004598) protocol with 30 Gy in 12 fractions and dose to 98% of the hippocampus ≤ 9 Gy and to 2% ≤ 17 Gy. WBRT was mainly performed with 35 Gy in 14 fractions or 30 Gy in 10 fractions. Anatomical images were segmented and the hippocampal volume was quantified using the Computational Anatomy Toolbox (CAT), including neuroradiological expert review of the segmentations.

Results: After statistically controlling for confounding variables such as age, gender, and total intracranial volume, hippocampal atrophy was found after both WBRT and HA-WBRT ( < 10). However, hippocampal decline across time following HA-WBRT was approximately three times lower than following conventional WBRT ( < 10), with an average atrophy of 3.1% 8.5% in the first 2 years after radiation therapy, respectively.

Conclusion: HA-WBRT is a therapeutic option for patients with multiple brain metastases, which can effectively and durably minimize hippocampal atrophy compared to conventional WBRT.
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http://dx.doi.org/10.3389/fonc.2021.714709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417356PMC
August 2021

In Regard to Alcorn et al.

Authors:
Carsten Nieder

Int J Radiat Oncol Biol Phys 2021 06;110(2):612-614

Department of Oncology and Palliative Medicine, Nordland Hospital Trust, Bodø, Norway; Department of Clinical Medicine, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsø, Norway.

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http://dx.doi.org/10.1016/j.ijrobp.2020.12.055DOI Listing
June 2021

New clinical data on human spinal cord re-irradiation tolerance.

Strahlenther Onkol 2021 Jun 5;197(6):463-473. Epub 2021 May 5.

Department of Oncology and Palliative Medicine, Nordland Hospital Trust, 8092, Bodø, Norway.

Purpose: To provide additional clinical data about the re-irradiation tolerance of the spinal cord.

Methods: This was a retrospective bi-institutional study of patients re-irradiated to the cervical or thoracic spinal cord with minimum follow-up of 6 months. The maximum dose (Dmax) and dose to 0.1cc (D0.1cc) were determined (magnetic resonance imaging [MRI]-defined cord) and expressed as equivalent dose in 2‑Gy fractions (EQD2) with an α/β value of 2 Gy.

Results: All 32 patients remained free from radiation myelopathy after a median follow-up of 12 months. Re-irradiation was performed after 6-97 months (median 15). In 22 cases (69%) the re-irradiation spinal cord EQD2 Dmax was higher than that of the first treatment course. Forty-eight of 64 treatment courses employed fraction sizes of 2.5 to 4 Gy to the target volume. The median cumulative spinal cord EQD2 Dmax was 80.7 Gy, minimum 61.12 Gy, maximum 114.79 Gy. The median cumulative spinal cord D0.1cc EQD2 was 76.1 Gy, minimum 61.12 Gy, maximum 95.62 Gy. Besides cumulative dose, other risk factors for myelopathy were present (single-course Dmax EQD2 ≥51 Gy in 9 patients, single-course D0.1cc EQD2 ≥51 Gy in 5 patients).

Conclusion: Even patients treated to higher cumulative doses than previously recommended, or at a considerable risk of myelopathy according to a published risk score, remained free from this complication, although one must acknowledge the potential for manifestation of damage in patients currently alive, i.e., still at risk. Individualized decisions to re-irradiate after appropriate informed consent are an acceptable strategy, including scenarios where low re-irradiation doses to the spinal cord would compromise target coverage and tumor control probability to an unacceptable degree.
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http://dx.doi.org/10.1007/s00066-021-01772-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154818PMC
June 2021

Validation of a Graded Prognostic Model in Patients With Brain Metastases Treated With Whole-brain Radiotherapy Instead of Radiosurgery.

In Vivo 2021 May-Jun;35(3):1569-1572

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Background/aim: The aim of this study was to analyze the survival predictions obtained from a recent graded prognostic model developed and validated in Japan.

Patients And Methods: This was a retrospective single-institution analysis of 249 patients, managed with whole-brain radiotherapy for brain metastases. The sum of scores was calculated as in the Japanese study. The following parameters were included: number of brain metastases, volume of the largest lesion, sex, Karnofsky performance status, primary cancer type, control of primary cancer, and presence of extra-cerebral metastases.

Results: Median overall survival was 3.0 months (95% CI= 2.6-3.4 months). The median sum of scores was 12, range=0-29. Statistically significant differences were observed between all prognostic strata.

Conclusion: The graded prognostic model is also applicable to patients treated with whole-brain rather than stereotactic radiotherapy.
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http://dx.doi.org/10.21873/invivo.12412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193299PMC
June 2021

Palliative Thoracic Radiotherapy for Non-Small Cell Lung Cancer in Outpatients: Reasons for Unplanned Hospitalization and Its Impact on Survival.

J Clin Med Res 2021 Mar 19;13(3):177-183. Epub 2021 Mar 19.

Department of Oncology and Palliative Medicine, Nordland Hospital, 8092 Bodo, Norway.

Background: The aims of the study were to examine the rates of and reasons for unplanned hospitalization after start of palliative radiotherapy or chemoradiation (CRT), and to study whether unplanned hospitalization deteriorates patients' prognosis. In addition, risk factors were identified.

Methods: A retrospective review of 136 patients treated with palliative radiotherapy or CRT was performed. Inclusion criteria were prescribed total dose at least 30 Gy and outpatient at the start of treatment. Uni- and multivariate analyses were employed.

Results: Fifty-eight patients (43%) were hospitalized within 3 months from start of radiotherapy or CRT. Their median overall survival was 6.7 months as compared to 11.1 months in non-hospitalized patients (P = 0.09). The median length of hospitalization was 8 days (range 1 - 61). In patients with possibly treatment-related hospitalization (n = 32), median survival was 5.0 months, significantly shorter than the 11.1 months observed in the remaining patients (P = 0.006). In multivariate analysis, only one variable was significantly associated with higher risk of unplanned hospitalization: previous hospitalization in the last 4 weeks before commencing radiotherapy or CRT.

Conclusions: Unplanned hospitalization occurred frequently in a standard care setting without early involvement of a dedicated palliative team. Patients with preceding hospitalization might represent a group that is particularly vulnerable, thus qualifying for a targeted intervention aiming at continued outpatient care.
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http://dx.doi.org/10.14740/jocmr4445DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016527PMC
March 2021

Symptom Burden in Patients Treated With Palliative Radiotherapy Before and During the COVID-19 Pandemic.

Anticancer Res 2021 Apr;41(4):1971-1974

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Background/aim: Oncological care has faced several challenges during the COVID-19 pandemic, e.g. treatment delay and worsening symptoms. Patient-reported anxiety, depression and sleep quality might have changed due to these special circumstances. Therefore, we analyzed the symptom burden of patients treated with palliative radiotherapy at our center.

Patients And Methods: A retrospective study was performed of 50 consecutive patients and the results were compared to those obtained in a previous pre-COVID study. The Edmonton Symptom Assessment Scale was employed to assess the preradiotherapy symptoms.

Results: The highest mean scores were reported for pain in activity (3.2) and dry mouth (3.1). Regarding anxiety, sadness/depression and sleep, the corresponding scores were 1.5, 1.2 and 2.7, respectively. Compared to the previous study, no significant increases were found. Most items had numerically lower mean values, e.g. anxiety (1.5 vs. 2.7). Both study populations had comparable median age (70.5 vs. 70 years), gender distribution and proportion of patients with bone metastases. However, there were two significant imbalances, namely a lower proportion of patients with prostate cancer (12 vs. 30%, p=0.02) and breast cancer (0 vs. 12%, p=0.02).

Conclusion: In patients who showed up for radiation treatment planning, the suspected increase in anxiety, sadness/depression and sleep disturbance was not demonstrable. It is not known whether or not patients with substantial worries chose to decline referral to palliative radiotherapy. Therefore, comprehensive large-scale studies of patterns of care are needed to fully understand the impact of COVID-19-related measures.
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http://dx.doi.org/10.21873/anticanres.14964DOI Listing
April 2021

Independent Validation of a Comprehensive Machine Learning Approach Predicting Survival After Radiotherapy for Bone Metastases.

Anticancer Res 2021 Mar;41(3):1471-1474

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Background/aim: The aim of this study was to analyze the survival predictions obtained from a web platform allowing for computation of the so-called Bone Metastases Ensemble Trees for Survival (BMETS). This prediction model is based on a machine learning approach and considers 27 prognostic covariates.

Patients And Methods: This was a retrospective single-institution analysis of 326 patients, managed with palliative radiotherapy for bone metastases. Deviations between model-predicted survival and observed survival were assessed.

Results: The median actuarial survival was 7.5 months. In total, 59% of patients survived for a period shorter than predicted. Twenty percent of the predictions of the median survival deviated from the observed survival by at least 6 months. Regarding actual survival <3 months (99 of 326 patients), the BMETS-predicted median survival was <3 months, i.e. correct in 67 of 99 cases (68%), whereas the model predicted a median of 4-6 months in 16 (16%) and of >6 months in another 16 cases.

Conclusion: The model predicted survival with high accuracy in a large number of patients. Nevertheless, if the model predicts a low likelihood of 3-month survival, actual survival may be very poor (often 1 month or less). Also, in patients who died within 3 months from the start of radiotherapy, the model often predicted longer survival (16% had >6 months predicted median survival). It would, therefore, be interesting to feed the U.S. database utilized to develop the BMETS with additional poor-prognosis patients to optimize the predictions.
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http://dx.doi.org/10.21873/anticanres.14905DOI Listing
March 2021

Assessment of extracranial metastatic disease in patients with brain metastases: How much effort is needed in the context of evolving survival prediction models?

Radiother Oncol 2021 06 4;159:17-20. Epub 2021 Mar 4.

Department of Radiation Oncology (MAASTRO Clinic), Maastricht University Medical Center, GROW, The Netherlands.

Survival prediction models may serve as decision-support tools for clinicians who have to assign the right treatment to each patient, in a manner whereby harmful over- or undertreatment is avoided as much as possible. Current models differ regarding their components, the overall number of components and the weighting of individual components. Some of the components are easy to assess, such as age or primary tumor type. Others carry the risk of inter-assessor inconsistency and time-dependent variation. The present publication focuses on issues related to assessment of extracranial metastases and potential surrogates, e.g. blood biomarkers. It identifies areas of controversy and provides recommendations for future research projects, which may contribute to prognostic models with improved accuracy.
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http://dx.doi.org/10.1016/j.radonc.2021.02.038DOI Listing
June 2021

An Institutional Audit of Maximum Heart Dose in Patients Treated With Palliative Radiotherapy for Non-small Cell Lung Cancer.

In Vivo 2021 Mar-Apr;35(2):955-958

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Background/aim: Recent studies suggested that high unintended radiation doses to the heart may reduce survival of patients with non-small-cell lung cancer (NSCLC) irradiated with curative intent. In the palliative setting, limited information is available. Therefore, we analyzed a single-institution cohort of 165 patients.

Patients And Methods: Patients in this retrospective study received palliative (chemo)radiotherapy (at least 30 Gy). Typical radiation doses were 10-13 fractions of 3 Gy and 15 fractions of 2.8 Gy. Heart dose constraints were not employed during treatment planning. The maximum dose to 1 cc of the heart was registered and converted into the equivalent dose in 2-Gy fractions (EQD2).

Results: The median heart dose (maximum to 1 cc) was 26 Gy (range=11-42 Gy). This dose corresponded to 28-108% of the prescription dose. After conversion into EQD2, the median maximum heart dose to 1 cc was 26 Gy, range=10-58 Gy). Neither higher T-stage nor higher N-stage predicted for higher maximum heart EQD2. The maximum heart EQD2 was not associated with overall survival.

Conclusion: The current practice of focusing on sparing of lungs and esophagus appears acceptable in the context of palliative regimes. To further strengthen this strategy, additional studies looking at cardiac substructures and other dosimetric variables such as mean dose are warranted.
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http://dx.doi.org/10.21873/invivo.12336DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8045074PMC
June 2021

Early High-Grade Thoracic Toxicity After Palliative Radiotherapy for Non-Small Cell Lung Cancer.

Cureus 2021 Jan 5;13(1):e12494. Epub 2021 Jan 5.

Oncology, Nordland Hospital Trust, Bodø, NOR.

Introduction: Palliative radiotherapy or chemoradiotherapy (CRT) for non-small cell lung cancer (NSCLC) may cause thoracic toxicities due to the radiation dose delivered to the lungs, heart, and esophagus. We studied severe thoracic toxicities resulting in hospitalization or death during the acute and sub-acute phase, i.e., three months from commencing radiotherapy. In addition, risk factors were identified.  Methods: A retrospective review of 165 patients treated with three-dimensional conformal palliative radiotherapy or CRT was performed. The prescribed total dose was equivalent to at least 30 Gy in 10 fractions. Uni- and multivariate analyses were employed.

Results: Twelve patients (7%) were hospitalized within three months from the start of radiotherapy or CRT. Six patients were hospitalized for esophagitis, three for dyspnea most likely caused by pneumonitis, and three for cardiac arrhythmia. Fatal toxicity was not observed. However, 19% of the 165 patients died from tumor-related causes during the time period of interest. In multivariate analysis, the only esophageal dose was significantly associated with the risk of hospitalization.  Conclusion: The safety profile of palliative radiotherapy or CRT in the acute and subacute phases was satisfactory. The hospitalization rate can be reduced by lowering the esophageal dose, as long as safe lung and heart doses can be maintained.
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http://dx.doi.org/10.7759/cureus.12494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861089PMC
January 2021

Recursive Partitioning Analysis of Systemic Therapy after Radiotherapy in Patients with Brain Metastases.

Oncol Res Treat 2021 21;44(3):86-92. Epub 2021 Jan 21.

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Purpose: The purpose of this study was to identify factors associated with the initiation or continuation of systemic treatment after brain irradiation. The outcome of interest was a utilization rate of at least 75%, given that active extracranial disease is common in patients with brain metastases. If left untreated, extracranial disease limits survival, regardless of successful local treatment of the brain metastases. In this context, systemic therapy has been shown to improve survival, e.g., after whole-brain radiotherapy.

Patients And Methods: The study included 185 patients with active extracranial disease, 60% of whom received systemic therapy.

Results: Survival from the start of brain irradiation was longest in patients who received additional immune checkpoint inhibitors, endocrine treatment, or anti-HER-2 drugs. After uni- and multivariate analyses, Eastern Cooperative Oncology Group performance status (PS) was selected as the first prediction criterion in the recursive partitioning analysis (RPA) decision tree analysis. RPA was successful for patients with PS 0-1, but patients with PS 2 had lower treatment utilization rates (maximum 60-70%, with a disease-dependent impact of age and LabBM score [blood test results]). The highest utilization rates were observed in (1) patients with PS 0 and (2) those with breast cancer, small-cell lung cancer, or lung adenocarcinoma with PS 1.

Conclusions: These results inform the multidisciplinary discussion and treatment planning for the common scenario of simultaneous intra- and extracranial metastases.
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http://dx.doi.org/10.1159/000513975DOI Listing
September 2021

Radiate Once More.

Int J Radiat Oncol Biol Phys 2021 02;109(2):314-315

Department of Radiation Oncology, University Hospital Freiburg, Freiburg, Germany.

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http://dx.doi.org/10.1016/j.ijrobp.2019.05.068DOI Listing
February 2021

Palliative Thoracic Radiotherapy for Non-small Cell Lung Cancer: Is There any Impact of Target Volume Size on Survival?

Anticancer Res 2021 Jan;41(1):355-358

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Background/aim: Recent studies suggested that target volume size impacts survival in patients with non-small cell lung cancer (NSCLC) receiving radical radiotherapy. Little is known about the impact of target volume size in palliative radiotherapy or chemoradiotherapy. Therefore, we analyzed the overall survival stratified for clinical and planning target volume (CTV and PTV) size.

Patients And Methods: A retrospective study of 77 patients who received palliative (chemo)radiotherapy (at least 30 Gy) for non-metastatic NSCLC, largely stage III was performed. Typical radiation doses were 10-13 fractions of 3 Gy and 15 fractions of 2.8 Gy.

Results: Median survival was 12 months (2-year rate 18%). Three prognostic factors emerged in the multivariate analysis. Hospitalization in the last 4 weeks before radiotherapy increased the hazard of death by a factor of 2.8 (p=0.002). Presence of a T1 or 2 tumor decreased the hazard of death by a factor of 0.5 (p=0.03). Concomitant chemoradiotherapy decreased the hazard of death by a factor of 0.4 (p=0.003).

Conclusion: Target volume size was not significantly associated with survival, suggesting that large size should not preclude palliative (chemo)radiotherapy as long as normal tissue dose constraints can be met.
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http://dx.doi.org/10.21873/anticanres.14783DOI Listing
January 2021

Neurological Death After Radiotherapy for Brain Metastases: Role of the LabBM Score.

Anticancer Res 2021 Jan;41(1):341-345

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Background/aim: The aim of this study was to identify patients at high risk of death from neurological cause because these patients may be appropriate candidates for intense brain-directed treatment, in contrast to patients with uncontrollable extracranial disease, inevitably leading to death. In this context, the LabBM score (endpoint: overall survival; five blood test results; often abnormal in patients with widespread disease) may be a relevant tool.

Patients And Methods: This was a retrospective single-institution analysis of 101 patients, managed with upfront brain irradiation. Associations between neurological death and different baseline and treatment parameters were assessed.

Results: A LabBM score of 0 (five normal blood test results) was present in 32% of patients. Neurological death was recorded in 27%. Seven parameters were associated with neurological death, including the LabBM score (univariate analyses). Three out of the seven were significantly associated with neurological death in the multi-nominal logistic regression analysis. The most important parameter was primary tumor type (colorectal or melanoma), with a hazard ratio of 14.3. Patients without liver metastases were also more likely to die from neurological causes. Finally, patients who did not receive additional systemic therapy were more likely to die from central nervous system progression. The median survival time was 3.9 months (entire cohort). When censoring patients who died from extracranial progression, the median time to neurological death was 17.4 months.

Conclusion: The LabBM score was not suitable for prediction of neurological death, in contrast to three other parameters. Interestingly, additional systemic therapy reduced the risk of neurological death, possibly because several new agents have known antitumor activity in the brain.
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http://dx.doi.org/10.21873/anticanres.14781DOI Listing
January 2021

Palliative Radiotherapy During the Last Month of Life: Have COVID-19 Recommendations Led to Reduced Utilization?

In Vivo 2021 Jan-Feb;35(1):649-652

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

Background/aim: The study aimed to evaluate practice changes in the time period of the early wave of the COVID-19 pandemic.

Patients And Methods: This was a retrospective single institution study. We defined palliative radiotherapy (PRT) initiated before Saturday, March 14 as pre-COVID and PRT initiated later as during-COVID (through June 30).

Results: National COVID-19 recommendations led to a significant decrease in PRT with 10 or more fractions, while re-irradiation and radiotherapy during the final 30 days of life were equally common before and after these recommendations had been issued in March 2020.

Conclusion: Rapid adoption of modified PRT regimens was feasible. However, the challenge of overtreatment in the final phase of the disease, due to inaccurate survival prediction, persisted.
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http://dx.doi.org/10.21873/invivo.12304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880726PMC
January 2021

Expansion of the LabBM Score: Is the LabPS the Best Tool Predicting Survival in Patients With Brain Metastases?

Am J Clin Oncol 2021 02;44(2):53-57

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø.

Objectives: The objective of this study were to improve the 3-tiered, purely biomarker-based LabBM score, which predicts the survival of patients with brain metastases, by adding the well-established prognostic factor performance status (PS), and to define its role in comparison with the recently proposed Extracranial-Graded Prognostic Assessment score, which is based on the well-known Diagnosis-specific Graded Prognostic Assessment and 2 of the same biomarkers.

Materials And Methods: This was a retrospective single-institution analysis of 212 patients, managed with upfront brain irradiation. Survival was stratified by LabBM and LabPS score. Each included serum hemoglobin, platelets, albumin, C-reactive protein, and lactate dehydrogenase (plus PS for the LabPS). Zero, 0.5, or 1 point was assigned and the final point sum calculated. A higher point sum indicates shorter survival.

Results: The new LabPS score predicted overall survival very well (median: 12.1 to 0.7 mo, 1-y rate: 52% to 0%), P=0.0001. However, the group with the poorest prognosis (3 or 3.5 points) was very small (4%). Most patients with comparably short survival had a lower point sum. The LabPS score failed to outperform the recently proposed Extracranial-Graded Prognostic Assessment score.

Conclusions: Integration of blood biomarkers should be considered when attempting to develop improved scores. Additional research is needed to improve the tools which predict short survival, because many of these patients continue to go undetected with all available scores.
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http://dx.doi.org/10.1097/COC.0000000000000784DOI Listing
February 2021

[Timing of androgen-deprivation therapy and radical radiotherapy in localized prostate cancer: a phase III randomized controlled trial].

Authors:
Carsten Nieder

Strahlenther Onkol 2020 Aug;196(8):738-739

Dept. of Oncology and Palliative Medicine, Nordland Hospital Trust, P.O. Box 1480, 8092, Bodø, Norwegen.

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http://dx.doi.org/10.1007/s00066-020-01645-5DOI Listing
August 2020

Adverse events in deceased hospitalised cancer patients as a measure of quality and safety in end-of-life cancer care.

BMC Palliat Care 2020 Jun 1;19(1):76. Epub 2020 Jun 1.

Institute of Community Medicine, The Arctic University of Norway, PO Box 6, 9038, Tromsø, Norway.

Background: Anticancer treatment exposes patients to negative consequences such as increased toxicity and decreased quality of life, and there are clear guidelines recommending limiting use of aggressive anticancer treatments for patients near end of life. The aim of this study is to investigate the association between anticancer treatment given during the last 30 days of life and adverse events contributing to death and elucidate how adverse events can be used as a measure of quality and safety in end-of-life cancer care.

Methods: Retrospective cohort study of 247 deceased hospitalised cancer patients at three hospitals in Norway in 2012 and 2013. The Global Trigger Tool method were used to identify adverse events. We used Poisson regression and binary logistic regression to compare adverse events and association with use of anticancer treatment given during the last 30 days of life.

Results: 30% of deceased hospitalised cancer patients received some kind of anticancer treatment during the last 30 days of life, mainly systemic anticancer treatment. These patients had 62% more adverse events compared to patients not being treated last 30 days, 39 vs. 24 adverse events per 1000 patient days (p < 0.001, OR 1.62 (1.23-2.15). They also had twice the odds of an adverse event contributing to death compared to patients without such treatment, 33 vs. 18% (p = 0.045, OR 1.85 (1.01-3.36)). Receiving follow up by specialist palliative care reduced the rate of AEs per 1000 patient days in both groups by 29% (p = 0.02, IRR 0.71, CI 95% 0.53-0.96).

Conclusions: Anticancer treatment given during the last 30 days of life is associated with a significantly increased rate of adverse events and related mortality. Patients receiving specialist palliative care had significantly fewer adverse events, supporting recommendations of early integration of palliative care in a patient safety perspective.
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http://dx.doi.org/10.1186/s12904-020-00579-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265218PMC
June 2020

Radiotherapy for nonagenarians: the value of biological versus chronological age.

Radiat Oncol 2020 May 19;15(1):113. Epub 2020 May 19.

Department of Radiation Oncology, University of Freiburg - Medical Center, Robert-Koch-Str. 3, 79106, Freiburg, Germany.

Background: The number of nonagenarian cancer patients (≥ 90 years) is continuously increasing, and radiotherapy is performed in a relevant proportion of patients, as surgery and chemotherapy are often not feasible for these patients. However, the evidence regarding the feasibility and treatment outcomes after radiotherapy for this patient group is very limited.

Methods: All nonagenarian patients receiving (chemo) radiotherapy between 2009 and 2019 at the University of Freiburg - Medical Center were analyzed for patterns of care, overall survival (OS) and therapy-associated toxicities according to the Common Terminology Criteria for Adverse Events. Uni- and multivariate Cox regression analyses were conducted to assess the influence of patient- and treatment-related factors on patient outcomes.

Results: One hundred nineteen patients with a total of 137 irradiated lesions were included in this analysis. After a median follow-up of 27 months, median OS was 10 months with a 3-year OS amounting to 11.1%. Univariate analyses demonstrated that a reduced performance status (HR = 1.56, 95% CI 1.00-2.45, p < 0.05), a higher burden of comorbidities (HR = 2.00, 95% CI 1.00-4.10, p < 0.05) and higher UICC tumor stages (HR = 2.21, 95% CI 1.14-4.26, p < 0.05) were associated with impaired survival rates. Split-course treatments (HR = 2.05, 95% CI 1.07-3.94, p < 0.05), non-completion of radiotherapy (HR = 7.17, 95% CI 3.88-13.26, p < 0.001) and palliative treatments (HR = 2.84, 95% CI 1.68-4.81, p < 0.05) were found to result in significantly reduced OS. In the multivariate analysis, split-course concepts (HR = 2.21, 95% CI 1.10-4.37, p < 0.05) and palliative treatments (HR = 3.19, 95% CI 1.77-5.75, p < 0.001) significantly deteriorated outcomes, while impaired ECOG status (HR = 1.49, 95% CI 0.91-2.43, p = 0.11) did not. The vast majority of patients reported either no (n = 40; 33.6%) or grade 1-2 acute toxicities (n = 66; 55.5%), and only very few higher-grade toxicities were observed in our study.

Conclusion: Radiotherapy for nonagenarian patients is generally feasible and associated with a low toxicity profile. Given the relatively poor OS rates and the importance of the quality of life for this patient group, individualized treatment regimens including hypofractionation concepts should be considered.
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http://dx.doi.org/10.1186/s13014-020-01563-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236131PMC
May 2020

Altered fractionation short-course radiotherapy for stage II-III rectal cancer: a retrospective study.

Radiat Oncol 2020 May 14;15(1):111. Epub 2020 May 14.

Department of Radiation Oncology, Ordensklinikum Linz Barmherzige Schwestern, Seilerstätte 4, 4010, Linz, Austria.

Purpose: To report the long-term outcomes of neoadjuvant altered fractionation short-course radiotherapy in 271 consecutive patients with stage II-III rectal cancer.

Patients And Methods: This was a retrospective single institution study with median follow-up of 101 months (8.4 years). Patients who were alive at the time of analysis in 2018 were contacted to obtain functional outcome data (phone interview). Radiotherapy consisted of 25 Gy in 10 fractions of 2.5 Gy administered twice daily. Median time interval to surgery was 5 days.

Results: Local relapse was observed in 12 patients (4.4%) after a median of 28 months. Overall survival after 5 and 10 years was 73 and 55.5%, respectively (corresponding disease-free survival 65.5 and 51%). Of all patients without permanent stoma, 79% reported no low anterior resection syndrome (LARS; 0-20 points), 9% reported LARS with 21-29 points and 12% serious LARS (30-42 points).

Conclusion: The present radiotherapy regimen was feasible and resulted in low rates of local relapse. Most patients reported good functional outcomes.
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http://dx.doi.org/10.1186/s13014-020-01566-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7227338PMC
May 2020

LabBM Score and Extracranial Score As New Tools for Predicting Survival in Patients with Brain Metastases Treated with Focal Radiotherapy.

Cureus 2020 Apr 11;12(4):e7633. Epub 2020 Apr 11.

Oncology, Nordland Hospital Trust, Bodø, NOR.

Background Two recently validated, untraditional prognostic scores include serum albumin and lactate dehydrogenase, among other parameters. The latter are hemoglobin, platelet counts, and C-reactive protein (three-tiered LabBM score), whereas the four-tiered extracranial score includes more than one extracranial site of metastatic involvement. Until now, head-to-head comparisons of these two scores in patients treated with focal radiotherapy for newly diagnosed brain metastases are not available. Methods This was a retrospective single-institution analysis of 51 patients, most of whom were managed with first-line stereotactic radiosurgery (SRS). Survival was stratified by the LabBM score and extracranial score. Results Both scores predicted survival, but the analyses were hampered by small subgroups. In particular, very few patients belonged to the unfavorable groups. Survival shorter than two months, which was recorded in 14%, was not well predicted by the LabBM score and extracranial score. Conclusions Very few patients treated with focal radiotherapy (largely SRS) had unfavorable prognostic features according to the two untraditional scores, which do not include the number of brain metastases and performance status. Additional research is needed to improve the tools that predict short survival because overtreatment during the terminal phase of metastatic disease continues to represent a relevant issue.
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http://dx.doi.org/10.7759/cureus.7633DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213767PMC
April 2020

Risk factors for esophagitis after hypofractionated palliative (chemo) radiotherapy for non-small cell lung cancer.

Radiat Oncol 2020 May 1;15(1):91. Epub 2020 May 1.

Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway.

Introduction: Esophagitis influences quality of life and might cause treatment interruption and hospitalization. Previous studies of risk factors focused on curative treatment for non-small cell lung cancer (NSCLC), which often involves concomitant chemoradiation (CRT). Given the uncertainty around extrapolation of dose constraints, we analyzed risk factors in patients treated with hypofractionated palliative regimens.

Patients And Methods: A retrospective review of 106 patients treated with palliative radiotherapy or CRT between 2009 and 2017 was performed.

Inclusion Criteria: prescribed total dose 30-54 Gy, dose per fraction 2.5-4 Gy, esophageal dose > 1 Gy. Uni- and multivariate analyses were performed in 97 eligible patients to identify predictive factors for acute esophagitis grade ≥ 1 (CTCAE 5.0).

Results: Forty percent of patients were treated with 15 fractions of 2.8 Gy (42 Gy) and 28% also received chemotherapy according to the CONRAD study regimen (induction and concomitant Carboplatin/Vinorelbine) published by the Norwegian Lung Cancer Group. Thirty-four percent were treated with 10 fractions of 3 Gy. Stage IV NSCLC was present in 47%. Esophagus Dmax was 39 Gy (population median) and Dmean 15 Gy. Overall 31% of patients developed esophagitis (26% grade 2-3, no grade 4-5). Several dosimetric parameters correlated with the risk of esophagitis (Dmax, Dmean, D5cc, V20, V30, V35, V40). Dmax outperformed other dosimetric variables in multivariate analysis. Furthermore, concomitant chemotherapy significantly increased the risk of esophagitis, while oral steroid medication reduced it. In patients with Dmax ≥40 Gy a reduced Dmean (≤20 Gy) was beneficial.

Conclusion: In order to reduce esophagitis after hypofractionated palliative treatment lower doses than those recommended in curative NSCLC settings are preferable. Besides esophageal dose, CRT is the main risk factor for esophagitis. Additional work is needed to confirm that steroids are able to modify the risk (or to rule out confounding effects of baseline variables not included in our database).
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http://dx.doi.org/10.1186/s13014-020-01550-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195792PMC
May 2020

External Validation of a Prognostic Score for Patients with Brain Metastases: Extended Diagnosis-Specific Graded Prognostic Assessment.

Oncol Res Treat 2020 26;43(5):221-227. Epub 2020 Mar 26.

Department of Radiation Oncology, University Hospital Würzburg, Würzburg, Germany.

Purpose: The aim of our study was the external validation of an extended variant of the four-tiered diagnosis-specific graded prognostic assessment (DS-GPA) that includes more information about extracranial disease burden and blood test results, and predicts survival of patients with brain metastases. The extracranial DS-GPA (EC-GPA) includes serum albumin, lactate dehydrogenase, and number of extracranial organs involved. Originally, the score was developed in Germany.

Patients And Methods: A retrospective analysis of 236 patients with brain metastases treated with primary whole-brain radiotherapy in North-Norway was performed (independent external validation cohort).

Results: The four-tiered EC-GPA score showed good discrimination between all prognostic groups (log-rank test p < 0.05 for all pairwise comparisons). One-year survival was 0, 11, 30, and 100%, respectively. Median survival was 0.7 months (95% CI, 0.5-0.9) in the worst prognostic group, with a hazard ratio for death of 44.31 (95% CI, 5.78-339.50) compared to the best group. In the German database, the corresponding HR was 31.64 (median survival 0.4 months). The remaining hazard ratios in this validation study were 7.13 and 12.10, compared with 4.84 and 9.26 in the score development study.

Conclusions: This study provides an independent validation of the EC-GPA, which was the best prognostic model for defining patients who did not benefit from radiation therapy of brain metastases in terms of overall survival in the original German study. The proposed modification of the established DS-GPA should undergo further validation in multi-institutional databases.
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http://dx.doi.org/10.1159/000506954DOI Listing
September 2020

Initial Experience after Transition to Immune Checkpoint Inhibitors in Patients with Non-small Cell Lung Cancer Treated in a Rural Healthcare Region.

Cureus 2020 Feb 18;12(2):e7030. Epub 2020 Feb 18.

Internal Medicine, Nordland Hospital Trust, Bodø, NOR.

Objective The aim of this study was to investigate the patterns of palliative care, terminal care, and hospital deaths in deceased patients with non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). Methods This study involves a retrospective analysis of a group of 32 patients treated with first- or second-line ICI regimens. The group was compared with a matched contemporary cohort of patients who received systemic treatment that did not include an ICI. The 1:1 matching was based on sex, age, stage of cancer (IV versus lower), and initial treatment after diagnosis (locoregional versus systemic). Results The median overall survival from diagnosis was 9.8 months [95% confidence interval (CI): 7.4-12.2 months] in the non-ICI patients and 11.6 months (95% CI: 5.9-17.3 months) in the ICI group (p: 0.09). Death resulting from toxicity was recorded in two patients (non-ICI) and one patient (ICI), respectively (p: 0.8). Hospital death was more common after ICI (19 versus 11 patients, p: 0.08). During the last three months of life, non-ICI patients spent a median of 11 days (range: 0-28) in the hospital, compared with 20 days (range: 0-45) for ICI patients (p: 0.005). More ICI patients (21 versus 14) received systemic therapy during the last three months of life (p: 0.13). However, treatment rates during the last four weeks were comparable (eight non-ICI and six ICI patients, respectively; p: 0.8). Conclusion We did not identify any concerns regarding the fatal toxicity of ICI treatment. Due to several different baseline parameters, there are reasons to believe that hospitalization and hospital death in the ICI group were mainly related to unevenly distributed disease characteristics and not to ICI administration itself. Since real-world data from rural patient cohorts might differ from those obtained in clinical trials, it is necessary to conduct additional and larger studies about ICI-associated patterns of terminal care.
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http://dx.doi.org/10.7759/cureus.7030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081957PMC
February 2020

Long-term survival results after treatment for oligometastatic brain disease.

Rep Pract Oncol Radiother 2020 May-Jun;25(3):307-311. Epub 2020 Mar 4.

Department of Radiation Oncology, University Hospital Freiburg, 79106 Freiburg, Germany.

Aim: The aim of this study was to characterize the survival results of patients with up to four brain metastases after intense local therapy (primary surgery or stereotactic radiotherapy) if extracranial metastases were absent or limited to one site, e.g. the lungs.

Background: Oligometastatic disease has repeatedly been reported to convey a favorable prognosis.

Material And Methods: This retrospective study included 198 German and Norwegian patients treated with individualized approaches, always including brain radiotherapy. Information about age, extracranial spread, number of brain metastases, performance status and other variables was collected. Uni- and multivariate tests were performed.

Results: Median survival was 16.5 months (single brain metastasis) and 9.8 months (2-4, comparable survival for 2, 3 and 4), respectively (p = 0.001). After 5 years, 15 and 2% of the patients were still alive. In patients alive after 2 years, added median survival was 23 months and the probability of being alive 5 years after treatment was 26%. In multivariate analysis, extracranial metastases were not significantly associated with survival, while primary tumor control was.

Conclusion: Long-term survival beyond 5 years is possible in a minority of patients with oligometastatic brain disease, in particular those with a single brain metastasis. The presence of extracranial metastases to one site should not be regarded a barrier towards maximum brain-directed therapy.
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http://dx.doi.org/10.1016/j.rpor.2020.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078502PMC
March 2020

Is there a seasonal variation of survival after systemic chemotherapy for metastatic castration-resistant prostate cancer in a rural part of North Norway?

Int J Circumpolar Health 2020 12;79(1):1742520

Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.

The winter darkness or polar night induces endocrine and metabolic mechanisms, which might reduce the efficacy of cancer treatment and thus contribute to shorter survival. Moreover, season-and weather-related treatment delays and irregularities might also cause reduced efficacy of anti-cancer drugs. Therefore, this study evaluated the prognostic impact of timing of chemotherapy (start during winter darkness or outside of this season), in terms of overall survival, in patients with metastatic castration-resistant prostate cancer (MCRPC) who received oncology care at the Nordland hospital Bodø. The study included 111 patients treated with first-line docetaxel chemotherapy for MCRPC. Twenty patients (18%) started their treatment during winter darkness (arbitrarily defined as ±4 weeks around 21 December). In unadjusted univariate analysis, survival was shorter in this group (median 10.2 vs. 18.9 months, p = 0.055). However, not all baseline parameters were equally distributed between the two groups. In multivariable-adjusted Cox regression analysis accounting for several confounding variables, only one factor was statistically significant: pre-chemotherapy serum lactate dehydrogenase level (a surrogate marker of disease burden). Thus, the present results suggest that seasonal variation is not a major contributor to the diverging survival outcomes observed after docetaxel chemotherapy.
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http://dx.doi.org/10.1080/22423982.2020.1742520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144237PMC
December 2020

Hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost for multiple brain metastases.

Cancer 2020 06 6;126(11):2694-2703. Epub 2020 Mar 6.

Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

Background: The current study was aimed at investigating the feasibility of hippocampus-avoidance whole-brain radiation therapy with a simultaneous integrated boost (HA-WBRT+SIB) for metastases and at assessing tumor control in comparison with conventional whole-brain radiation therapy (WBRT) in patients with multiple brain metastases.

Methods: Between August 2012 and December 2016, 66 patients were treated within a monocentric feasibility trial with HA-WBRT+SIB: hippocampus-avoidance WBRT (30 Gy in 12 fractions, dose to 98% of the hippocampal volume ≤ 9 Gy) and a simultaneous integrated boost (51 or 42 Gy in 12 fractions) for metastases/resection cavities. Intracranial tumor control, hippocampal failure, and survival were subsequently compared with a retrospective cohort treated with WBRT via propensity score matching analysis.

Results: After 1:1 propensity score matching, there were 62 HA-WBRT+SIB patients and 62 WBRT patients. Local tumor control (LTC) of existing metastases was significantly higher after HA-WBRT+SIB (98% vs 82% at 1 year; P = .007), whereas distant intracranial tumor control was significantly higher after WBRT (82% vs 69% at 1 year; P = .016); this corresponded to higher biologically effective doses. Intracranial progression-free survival (PFS; 13.5 vs 6.4 months; P = .03) and overall survival (9.9 vs 6.2 months; P = .001) were significantly better in the HA-WBRT+SIB cohort. Four patients (6.5%) developed hippocampal metastases after hippocampus avoidance. The neurologic death rate after HA-WBRT+SIB was 27.4%.

Conclusions: HA-WBRT+SIB can be an efficient therapeutic option for patients with multiple brain metastases and is associated with improved LTC of existing metastases, higher intracranial PFS, a reduction of the neurologic death rate, and an acceptable risk of radiation necrosis. The therapy has the potential to prevent neurocognitive adverse effects, which will be further evaluated in the multicenter, phase 2 HIPPORAD trial.
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http://dx.doi.org/10.1002/cncr.32787DOI Listing
June 2020
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