CT-Defined Fat Index Is a Prognostic Factor of Chronic Graft-Versus-Host Disease Outcomes in Adult Allogeneic Transplant Recipients
Bibliographic record
Abstract
BackgroundAdditional tools for risk-stratification of chronic graft vs. host disease (cGVHD) may enhance the established NIH consensus-based severity score. Radiographic body composition metrics arising from standardly performed CT-scans have previously shown significant association with treatment complications in other cancer populations. We aimed to characterize skeletal muscle (SM) and adiposity in cGVHD patients to discern potential association with subsequent mortality.MethodsA consecutive retrospective series of patients who underwent allogeneic hematopoietic cell transplantation (HCT) at our center from 2005-2016 and had the following criteria were evaluated: 1) diagnosis of either non-Hodgkin (NHL) or Hodgkin Lymphoma (HL) to enrich for available CT, and 2) had a history of cGVHD. Skeletal muscle index (SMI) and fat index (FI) were quantified on CT imaging at the 3rd lumbar (L3) and 4th thoracic (T4) vertebra. SM Hounsfield units (HU) were obtained to evaluate SM density. Cut points for SMI and FI were done via gender specific optimal stratification.ResultsA total of n=115 patients met the inclusion criteria for this analysis. The median age was 52 (range 22-69), and patients were predominantly male (n=71, 62%) and diagnosed with NHL (n=110, 96%). Onset cGVHD NIH overall severity was mild in N= 56 (49%), moderate in 44 (38%), and severe in 15 (13%). When considering all body composition parameters, high L3 fat index (FI) at D100 was associated with worsened OS (HR 2.83, 95% CI 1.30, 6.12, p=0.008), but SMI and SM HU were not associated with OS (p=NS). In multivariate analysis, high L3 FI was independently associated with increased mortality (HR 2.29, 95% CI 1.03-5.1, p=0.043) (Table 1), while SMI and HU were not (p=NS). In secondary analysis, we quantified the change in body composition in evaluable patients (n=72). Cachexia development was observed from pre- to post-HCT (median % weight change -5.5 [-50.1-13.3]. The majority of patients had decline in both FI and SMI (Figure 1). These changes were also seen in CT chest with high correlation between SMI and FI when comparing CT abdomen chest r=0.854 and r=0.798 respectively.ConclusionsIncreased FI is associated with worsened overall survival in cGVHD patients, while SMI and HU are not. These findings suggest that low skeletal muscle mass alone does not predict for poor outcomes in cGVHD as previously described in other cancers. Body composition analysis in a larger cGVHD cohort is needed to confirm these findings and examine risk-stratification within NIH severity groups. Additional tools for risk-stratification of chronic graft vs. host disease (cGVHD) may enhance the established NIH consensus-based severity score. Radiographic body composition metrics arising from standardly performed CT-scans have previously shown significant association with treatment complications in other cancer populations. We aimed to characterize skeletal muscle (SM) and adiposity in cGVHD patients to discern potential association with subsequent mortality. A consecutive retrospective series of patients who underwent allogeneic hematopoietic cell transplantation (HCT) at our center from 2005-2016 and had the following criteria were evaluated: 1) diagnosis of either non-Hodgkin (NHL) or Hodgkin Lymphoma (HL) to enrich for available CT, and 2) had a history of cGVHD. Skeletal muscle index (SMI) and fat index (FI) were quantified on CT imaging at the 3rd lumbar (L3) and 4th thoracic (T4) vertebra. SM Hounsfield units (HU) were obtained to evaluate SM density. Cut points for SMI and FI were done via gender specific optimal stratification. A total of n=115 patients met the inclusion criteria for this analysis. The median age was 52 (range 22-69), and patients were predominantly male (n=71, 62%) and diagnosed with NHL (n=110, 96%). Onset cGVHD NIH overall severity was mild in N= 56 (49%), moderate in 44 (38%), and severe in 15 (13%). When considering all body composition parameters, high L3 fat index (FI) at D100 was associated with worsened OS (HR 2.83, 95% CI 1.30, 6.12, p=0.008), but SMI and SM HU were not associated with OS (p=NS). In multivariate analysis, high L3 FI was independently associated with increased mortality (HR 2.29, 95% CI 1.03-5.1, p=0.043) (Table 1), while SMI and HU were not (p=NS). In secondary analysis, we quantified the change in body composition in evaluable patients (n=72). Cachexia development was observed from pre- to post-HCT (median % weight change -5.5 [-50.1-13.3]. The majority of patients had decline in both FI and SMI (Figure 1). These changes were also seen in CT chest with high correlation between SMI and FI when comparing CT abdomen chest r=0.854 and r=0.798 respectively. Increased FI is associated with worsened overall survival in cGVHD patients, while SMI and HU are not. These findings suggest that low skeletal muscle mass alone does not predict for poor outcomes in cGVHD as previously described in other cancers. Body composition analysis in a larger cGVHD cohort is needed to confirm these findings and examine risk-stratification within NIH severity groups.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".