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Crouzen JA, Mast ME, Hakstege M, Broekman MLD, Baladi C, Mertens BJA, Nandoe Tewarie RDS, Kerkhof M, Vos MJ, Maas KW, Souwer ETD, Wiggenraad RGJ, van der Voort van Zyp NCMG, Kiderlen M, Petoukhova AL, Zindler JD. External validation of the lung-molGPA to predict survival in patients treated with stereotactic radiotherapy for brain metastases of non-small cell lung cancer. Radiother Oncol 2024; 198:110405. [PMID: 38925263 DOI: 10.1016/j.radonc.2024.110405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2024] [Revised: 06/14/2024] [Accepted: 06/17/2024] [Indexed: 06/28/2024]
Abstract
BACKGROUND In the era of personalized medicine, individualized prognostic models with tumor characteristics are needed to inform patients about survival. Before clinical use, external validation of such models by an independent group is needed. An updated version of the graded prognostic assessment (GPA) estimates survival in patients with brain metastases (BMs) of non-small cell lung cancer (NSCLC). This is the first external validation of the updated Lung-molGPA in patients treated with stereotactic radiotherapy (SRT) for one or more BMs. MATERIALS AND METHODS Patients treated with SRT for BMs from NSCLC adenocarcinoma were retrospectively included. GPA score was calculated for each patient based on six prognostic factors including age, Karnofsky Performance Status, number of BMs, extracranial metastases, EGFR/ALK status, and PD-L1 expression. Kaplan-Meier analysis evaluated survival probability. Impact of individual prognostic factors on survival was assessed by univariate and multivariate analyses using the Cox proportional hazard model. Predictive performance was evaluated using discrimination (C-statistic) and calibration (Brier test). RESULTS The cohort (n = 241) was divided into four prognostic groups. Overall median survival was 15 months. Predicted and observed median survival were similar between the original and validation cohorts, apart from the most favorable prognostic group. With adequate C-statistics and Brier scores, the Lung-molGPA provided accurate survival predictions. CONCLUSION The Lung-molGPA accurately predicted survival in our European population, except for an overestimation of survival in the small most favorable prognostic group. This prognostic model was externally validated and is therefore useful for counseling of patients with BMs of NSCLC adenocarcinoma.
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Affiliation(s)
- Jeroen A Crouzen
- Department of Radiotherapy, Haaglanden Medical Center, The Hague, The Netherlands
| | - Mirjam E Mast
- Department of Radiotherapy, Haaglanden Medical Center, The Hague, The Netherlands
| | - Martijn Hakstege
- Department of Radiotherapy, Haaglanden Medical Center, The Hague, The Netherlands
| | - Marike L D Broekman
- Department of Neurosurgery, Haaglanden Medical Center, The Hague, The Netherlands; Department of Neurosurgery, Leiden University Medical Center, Leiden, The Netherlands
| | - Chaouki Baladi
- Department of Neurosurgery, Haaglanden Medical Center, The Hague, The Netherlands
| | - Bart J A Mertens
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
| | | | - Melissa Kerkhof
- Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands
| | - Maaike J Vos
- Department of Neurology, Haaglanden Medical Center, The Hague, The Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
| | - Klaar W Maas
- Department of Pulmonology, Haaglanden Medical Center, The Hague, The Netherlands
| | - Esteban T D Souwer
- Department of Medical Oncology, Haaglanden Medical Center, The Hague, The Netherlands
| | - Ruud G J Wiggenraad
- Department of Radiotherapy, Haaglanden Medical Center, The Hague, The Netherlands
| | | | - Mandy Kiderlen
- Department of Radiotherapy, Haaglanden Medical Center, The Hague, The Netherlands
| | - Anna L Petoukhova
- Department of Medical Physics, Haaglanden Medical Center, The Hague, The Netherlands
| | - Jaap D Zindler
- Department of Radiotherapy, Haaglanden Medical Center, The Hague, The Netherlands; Department of Radiotherapy, HollandPTC, Delft, The Netherlands.
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Ribeiro LM, Bomtempo FF, Rocha RB, Telles JPM, Neto EB, Figueiredo EG. Development and adaptations of the Graded Prognostic Assessment (GPA) scale: a systematic review. Clin Exp Metastasis 2023; 40:445-463. [PMID: 37819546 DOI: 10.1007/s10585-023-10237-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Accepted: 09/22/2023] [Indexed: 10/13/2023]
Abstract
The Graded Prognostic Assessment (GPA) score has the best accuracy among prognostic scales for patients with brain metastases (BM). A wide range of GPA-derived scales have been established to different types of primary tumor BM. However, there is a high variability between them, and their characteristics have not been described altogether yet. We aim to summarize the features of the existent GPA-derived scales and to compare their predictor factors and their uses in clinical setting. Medline was searched from inception until January 2023 to identify studies related to the development, update, or validation of GPA. The initial search yielded 1,083 results. 16 original studies and 16 validation studies were included, comprising a total of 33,348 patients. 13 different scales were assessed, including: GPA, Diagnosis-Specific GPA, Extracranial Score, Lung-molGPA, Updated Renal GPA, Updated Gastrointestinal GPA, Modified Breast GPA, Integrated Melanoma GPA, Melanoma Mol GPA, Sarcoma GPA, Hepatocellular Carcinoma GPA, Colorectal Cancer GPA, and Uterine Cancer GPA. The most prevalent prognostic predictors were age, Karnofsky Performance Status, number of BM, and presence or absence of extracranial metastases. Treatment modalities consisted of whole brain radiation therapy, stereotactic radiosurgery, surgery, cranial radiotherapy, gamma knife radiosurgery, and BRAF inhibitor therapy. Median survival rates with no treatment and with a specific treatment ranged from 6.1 weeks to 33 months and from 3.1 to 21 months, respectively. Original GPA and GPA-derived scales are valid prognostic tools, but with heterogeneous survival results when compared to each other. More studies are needed to improve scientific evidence of these scales.
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Affiliation(s)
| | | | | | | | - Eliseu Becco Neto
- Division of Neurosurgery, University of São Paulo, São Paulo, Brazil
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Palliative appropriateness criteria: external validation of a new method to evaluate the suitability of palliative radiotherapy fractionation. Strahlenther Onkol 2023; 199:278-283. [PMID: 36625853 PMCID: PMC9938013 DOI: 10.1007/s00066-022-02040-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2022] [Accepted: 12/12/2022] [Indexed: 01/11/2023]
Abstract
BACKGROUND Recently, the palliative appropriateness criteria (PAC) score, a novel metric to aid clinical decision-making between different palliative radiotherapy fractionation regimens, has been developed. It includes baseline parameters including but not limited to performance status. The researchers behind the PAC score analyzed the percent of remaining life (PRL) on treatment. The latter was accomplished by calculating the time between start and finish of palliative radiotherapy (minimum 1 day in case of a single-fraction regimen) and dividing it by overall survival in days from start of radiotherapy. The purpose of the present study was to validate this novel metric. PATIENTS AND METHODS The retrospective validation study included 219 patients (287 courses of palliative radiotherapy). The methods were identical to those employed in the score development study. The score was calculated by assigning 1 point each to several factors identified in the original study and using the online calculator provided by the PAC developers. RESULTS Median survival was 6 months and death within 30 days from start of radiotherapy was recorded in 13% of courses. PRL on treatment ranged from 1 to 23%, median 8%. Significant associations were confirmed between online-calculated PAC score, observed survival, and risk of death within 30 days from the start of radiotherapy. Patients with score 0 had distinctly better survival than all other groups. The score-predicted median risk of death within 30 days from start of radiotherapy was 22% in our cohort. A statistically significant correlation was found between predicted and observed risk (p < 0.001). The original and present study were not perfectly concordant regarding number and type of baseline parameters that should be included when calculating the PAC score. CONCLUSION This study supports the dual strategy of PRL and risk of early death calculation, with results stratified for fractionation regimen, in line with the original PAC score study. When considering multifraction regimens, the PAC score identifies patients who may benefit from shorter courses. Additional work is needed to answer open questions surrounding the underlying components of the score, because the original and validation study were only partially aligned.
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Nieder C, Stanisavljevic L, Aanes SG, Mannsåker B, Haukland EC. 30-day mortality in patients treated for brain metastases: extracranial causes dominate. Radiat Oncol 2022; 17:92. [PMID: 35551618 PMCID: PMC9097068 DOI: 10.1186/s13014-022-02062-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2022] [Accepted: 05/01/2022] [Indexed: 11/10/2022] Open
Abstract
Background Established prognostic models, such as the diagnosis-specific graded prognostic assessment, were not designed to specifically address very short survival. Therefore, a brain metastases-specific 30-day mortality model may be relevant. We hypothesized that in-depth evaluation of a carefully defined cohort with short survival, arbitrarily defined as a maximum of 3 months, may provide signals and insights, which facilitate the development of a 30-day mortality model. Methods Retrospective analysis (2011–2021) of patients treated for brain metastases with different approaches. Risk factors for 30-day mortality from radiosurgery or other primary treatment were evaluated. Results The cause of death was unrelated to brain metastases in 61%. Treatment-related death (grade 5 toxicity) did not occur. Completely unexpected death was not observed, e.g. accident, suicide or sudden cardiac death. Logistic regression analysis showed 9 factors associated with 30-day mortality (each assigned 3–6 points) and a point sum was calculated for each patient. The point sum ranged from 0 (no risk factors for death within 30 days present) to 30. The results can be grouped into 3 or 4 risk categories. Eighty-three percent of patients in the highest risk group (> 16 points) died within 30 days, and none survived for more than 2 months. However, many cases of 30-day mortality (more than half) occurred in intermediate risk categories. Conclusion Extracranial tumor progression was the prevailing cause of 30-day mortality and few, if any deaths could be considered relatively unexpected when looking at the complete oncological picture. We were able to develop a multifactorial prediction model. However, the model’s performance was not fully satisfactory and it is not routinely applicable at this point in time, because external validation is needed to confirm our hypothesis-generating findings.
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Affiliation(s)
- Carsten Nieder
- Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway. .,Department of Clinical Medicine, Faculty of Health Sciences, UiT-The Arctic University of Norway, Tromsö, Norway.
| | - Luka Stanisavljevic
- Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway
| | - Siv Gyda Aanes
- Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway
| | - Bård Mannsåker
- Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway
| | - Ellinor Christin Haukland
- Department of Oncology and Palliative Medicine, Nordland Hospital, 8092, Bodø, Norway.,Department of Quality and Health Technology, Faculty of Health Sciences, SHARE-Center for Resilience in Healthcare, University of Stavanger, Stavanger, Norway
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Gao QP, Yang DZ, Yuan ZB, Guo YX. Prognostic factors and its predictive value in patients with metastatic spinal cancer. World J Clin Cases 2021; 9:5470-5478. [PMID: 34307601 PMCID: PMC8281408 DOI: 10.12998/wjcc.v9.i20.5470] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2021] [Revised: 04/25/2021] [Accepted: 04/26/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The spine is the most common location of metastatic diseases. Treating a metastatic spinal tumor depends on many factors, including patients' overall health and life expectancy. The present study was conducted to investigate prognostic factors and clinical outcomes in patients with vertebral metastases. AIM To investigate prognostic factors and their predictive value in patients with metastatic spinal cancer. METHODS A retrospective analysis of 109 patients with metastatic spinal cancer was conducted between January 2015 and September 2017. The prognoses and survival were analyzed, and the effects of factors such as clinical features, treatment methods, primary lesions and affected spinal segments on the prognosis of patients with metastatic spinal cancer were discussed. The prognostic value of Frankel spinal cord injury functional classification scale, metastatic spinal cord compression (MSCC), spinal instability neoplastic score (SINS) and the revised Tokuhashi score for prediction of prognosis was explored in patients with metastatic spinal tumors. RESULTS Age, comorbidity of metastasis from elsewhere, treatment methods, the number of spinal tumors, patient's attitude toward tumors and Karnofsky performance scale score have an effect on the prognosis of patients (all P < 0.05). With respect to classification of spinal cord injury, before operation, the proportion of grade B and grade C was higher in the group of patients who died than in the group of patients who survived, and that of grade D and grade E was lower in the group of patients who died than in the group of patients who survived (all P < 0.05). At 1 mo after operation, the proportion of grade A, B and C was higher in the group of patients who died than in the group of patients who survived, and that of grade E was lower in patients in the group of patients who died than in the group of patients who survived (all P < 0.05). MSCC occurred in four (14.3%) patients in the survival group and 17 (21.0%) patients in the death group (P < 0.05). All patients suffered from intractable pain, dysfunction in spinal cord and even paralysis. The proportion of SINS score of 1 to 6 points was lower in the death group than in the survival group, and the proportion of SINS score of 7 to 12 points was higher in the death group than in the survival group (all P < 0.05). The proportion of revised Tokuhashi score of 0 to 8 points and 9 to 11 points were higher in the death group than in the survival group, and the proportion of revised Tokuhashi score of 12 to 15 points was lower in the death group than in the survival group (all P < 0.05). Frankel spinal cord injury functional classification scale, MSCC, SINS and revised Tokuhashi score were important factors influencing the surgical treatment of patients with metastatic spinal cancer (all P < 0.05). CONCLUSION Frankel spinal cord injury functional classification scale, MSCC, SINS and revised Tokuhashi score were helpful in predicting the prognosis of patients with metastatic spinal cancer.
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Affiliation(s)
- Qing-Peng Gao
- Department of Spine Surgery, The Second Clinical Medical College of Jinan University, Shenzhen 518020, Guangdong Province, China
| | - Da-Zhi Yang
- Department of Spine Surgery, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen 518020, Guangdong Province, China
| | - Zheng-Bin Yuan
- Department of Spine Surgery, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen 518020, Guangdong Province, China
| | - Yu-Xia Guo
- Department of Gynecology, Shenzhen People’s Hospital, 2nd Clinical Medical College of Jinan University, Shenzhen 518020, Guangdong Province, China
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Nieder C, Mannsåker B, Yobuta R. Validation of a Graded Prognostic Model in Patients With Brain Metastases Treated With Whole-brain Radiotherapy Instead of Radiosurgery. In Vivo 2021; 35:1569-1572. [PMID: 33910837 DOI: 10.21873/invivo.12412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 02/04/2021] [Accepted: 02/10/2021] [Indexed: 11/10/2022]
Abstract
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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Affiliation(s)
- Carsten Nieder
- Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway; .,Department of Clinical Medicine, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway
| | - Bård Mannsåker
- Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway
| | - Rosalba Yobuta
- Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway
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Expansion of the LabBM Score: Is the LabPS the Best Tool Predicting Survival in Patients With Brain Metastases? Am J Clin Oncol 2021; 44:53-57. [PMID: 33350680 DOI: 10.1097/coc.0000000000000784] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
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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Nieder C, Dalhaug A, Haukland E. Recursive Partitioning Analysis of Systemic Therapy after Radiotherapy in Patients with Brain Metastases. Oncol Res Treat 2021; 44:86-92. [PMID: 33477159 DOI: 10.1159/000513975] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2020] [Accepted: 12/21/2020] [Indexed: 11/19/2022]
Abstract
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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Affiliation(s)
- Carsten Nieder
- Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway, .,Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway,
| | - Astrid Dalhaug
- Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway
| | - Ellinor Haukland
- Department of Oncology and Palliative Medicine, Nordland Hospital, Bodø, Norway.,Department of Clinical Medicine, Faculty of Health Sciences, UiT, The Arctic University of Norway, Tromsø, Norway
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