Cancer-Associated Thrombosis: A Clinical Scoping Review of the Risk Assessment Models Across Solid Tumours and Haematological Malignancies

Figures & data

Table 1 Inclusion Criteria

Category	Inclusion Criteria
Language of publication	English
Year of publication	JAN 2008–JAN 2021
Publication type	Original research articles
Outcomes measures	Risk assessment model discriminative performance
Methodology	Studies of derivation, validation, or comparison of risk assessment models were eligible for inclusion
Patients	Ambulatory active cancer patients. Currently receiving chemotherapy or planned for chemotherapy

Table 2 RAM in Solid Organ Malignancy Components and Scores

Patients Characteristics	KRS	ONKOTEV Score	PROTECHT Score	CONKO Score	Vienna-CATS Score	TicOnco Score	New-CATS Score	COMPASS -CAT Score	The MDACC CAT
Pancreatic or gastric cancer (very high-risk tutors)	2	KRS ≥2= 1	2	2	2	2	Tumour site		Cancer type +
Lung, gynaecological, lymphoma, bladder, or testicular (high-risk tutors)	1		1	1	1	1
Prechemotherapy haemoglobin <110 g/L or use of erythropoietin	1		1	1	1	1
Prechemotherapy leucocyte count >11×10^9/L	1		1	1	1	1
Prechemotherapy platelet count >350 G/L	1		1	1	1	1		2
Body mass index ≥35 kg/m^2	1		1	-	1	1
Previous venous thromboembolism		1						1
Metastatic disease/advance		1						2	+
Vascular/lymphatic macroscopic compression (detected by MRI)		1
World Health Organization performance status >2				1
D-dimer>1.44 μg/L					1		+
Soluble P-selectin>53.1 ng/L					1
Single nucleotide polymorphism						1
Gemcitabine chemotherapy			1
Platinum-based chemotherapy			1						+
Use of erythrocyte stimulating agent (ESA)									+
Time since cancer diagnosis<6 months								4
Central venous catheter								3
Anti-hormonal therapy for women with hormone receptor + breast cancer or on anthracycline.								6
Cardiovascular risk factors/comorbidities (≥2 of the following: personal history of peripheral arterial disease, ischemic stroke, coronary artery disease, hypertension, hyperlipidaemia, diabetes melitis, obesity).								5
Hospitalization								5
	High risk ≥3, Intermediate risk 1–2, Low risk 0						Nomogram scaling	≤6:low/Intermediate,>7: high risk	Nomogram scaling

Figure 1 Flowchart for selecting the studies included in the scoping review.

Table 3 RAM in Solid Organ Malignancy; Populations, Statistics, Advantages, and Disadvantages

RAM (Year)	Population	Type of Malignancy	Parameters	C Statistics/ HR	Validation Cohort	Advantages/Disadvantages
Khorana risk score (2008)^Citation16	Derivation cohort, n = 2701 Validation cohort, n = 1365	Breast, Lung, Ovarian, Sarcoma, Colon, and Lymphomas	Site of cancer platelet count ≥350 x 10^9/L haemoglobin ≤100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count ≥11 x 10^9/L, body mass index (BMI) of 35 kg/m2 or more	0.7 for both cohorts	More than 55 validation cohorts and several systematic reviews.	Advantages: Good in classifying high-risk. -more predictive when considering a score of ≥2 as a cut-off point for high risk Disadvantages: Suboptimal performance in predicting VTE in low-risk groups
Vienna Cancer and Thrombosis Study (CATS) Score(2018)^Citation17	n = 819	Breast, Lung, Stomach, Colorectal, Pancreas, Kidney, Prostate, Brain, Lymphoma, Multiple myeloma	Adds soluble P-selectin and D-dimer to KRS	1.9 per 1 point increase	Comparison study with no statistical significance^Citation2*	Disadvantages: Applicability in p soluble monitoring in a real-life setting might not be feasible
New Vienna (CATSCORE)^Citation18	CATS cohort, n = 1423 MICA cohort, n = 832	Breast, Prostate, Lung, Colorectal, Esophagus, Kidney, Lymphoma, Bladder or urothelial, Uterine, Cervical, Ovarian, Pancreas, Stomach	Site of cancer and D-dimer	0.66 in CATS 0.68 in MICA	Comparison study with no statistical significance^Citation2*	Advantages: only two factors score Disadvantage: Suboptimal performance in the comparison trial
PROTECHT Score (2012)	Placebo arm, n = 381 Nadroparin arm, n = 769	Gastrointestinal, Lung, Breast, Ovary, Pancreas, Head and Neck	Add gemcitabine, cisplatin, or carboplatin therapy to KRS	NA	1 study with positive^Citation19 2 studies show poor performance^Citation2,Citation20	Advantages: easy to use, considers treatment-related risk factors Disadvantages: Suboptimal performance in the comparison trial
CONKO004(2015)^Citation21	n= 312	NA	Replace BMI in KRS with performance status	NA	Two comparison study with negative outcome*^Citation19,Citation20	Advantage: easy applicability Disadvantages: poor stratification performance
ONKOTEV Score(2017)^Citation22	n = 843		Khorana score >2, personal history of VTE, metastatic disease, vascular/lymphatic macroscopic compression	C-statistic:0.719 at 3 months 0.754 at 6 months HR: Score = 1: 3.29 Score = 2: 6.54 Score > 2: 13.74	Multiple validation and comparison trials with negative outcome.*^Citation2,Citation20	Advantages: easy to apply, consider tumour-related factors Disadvantages: Suboptimal performance
The COMPASS-CAT score(2016)^Citation23	n = 1023	Breast, Colorectal, Lung, or Ovarian cancer	Anthracycline or anti-hormonal therapy, time since cancer diagnosis, central venous catheter, stage of cancer, presence of cardiovascular risk factors, recent hospitalization for acute medical illness, personal history of VTE, and platelet count	C statistic: 0.850	Multiple validation.^Citation24^–^Citation27	Advantages: Good performance in lung carcinoma,^Citation24 moves from traditional KRS Disadvantages: poor calibration.
Tic-ONCO score(2018)^Citation28	n = 391		Adds genetic risk score to KS	C-statistic 0.73 HR = 1.69	NA	Disadvantages: Application of genetics in a real-life setting is questionable
The MDACC CAT model^Citation29	n= 548	Breast, Gastrointestinal non-pancreas, Pancreas, Genitourinary non-kidney Kidney, Gynaecological Lung and head/neck Lymphoma	Presence of metastasis, use of platinum-based chemotherapy, the use of ESAs and malignancies of origin in the gastrointestinal, gynecologic, and head-neck/lung organs	C-index: 0.74	NA	Advantages: readily available information Disadvantages: lack of external validation

Notes: *Comparison studies was done between Khorana, PROTECHT, CONKO, CATScore and ONKOTEV.

Abbreviations: MICA, Multinational Cohort Study; CATS, Vienna Cancer and thrombosis study; HR, hazards ratio; C-statistic /C-index, concordance statistic; NA, not available.

Table 4 Different RAM in Lung Carcinoma Components, Statistics, and Performances

RAM	KRS^Citation16	COMPASS-CAT^Citation23	ROADMAP‐CAT Biomarker Score^Citation26	COMPASS-CAT ROADMAP^Citation26	CANTARISK Score^Citation54
Parameters	Site of cancer platelet count ≥350 x 109/L haemoglobin ≤100 g/L (10 g/dL) and/or use of erythropoiesis stimulating agents, leukocyte count ≥11 x 10^9/L, body mass index of 35 kg/m^2 or more	Anthracycline or anti-hormonal therapy, time since cancer diagnosis, central venous catheter, stage of cancer, presence of CV risk factors platelet count, recent hospitalization of acute medical illness, personal VTE history	The procoagulant phospholipid‐dependent clotting time (Procoag‐PPL) and the mean rate index (MRI) of the propagation phase of thrombin generation assay	Procoag‐ PPL and MRI with the COMPASS‐CAT RAM	Older age, current or former smokers, chronic obstructive pulmonary disease, ECOG PS ≥2, no prior cancer surgery, and metastatic disease are predictive of VTE
Type	Pan cancerous	Breast, Colorectal, Lung or Ovarian cancer	Lung	Lung	Lung
Statistics	Unable to stratify (1.1; 95%-CI, 0.72–1.7)^Citation44	C statistic 0.89^Citation24	(NPV) 97% (PPV) 25%	(NPV) 97% (PPV) 70%	p<0.0001 awaiting validation
Performance	KRS underperformed in risk stratification in lung ca.	Excellent performance in small cohort, need large cohort validation	Applicability of special blood assays in real life setting need to be considered	Applicability of special blood assays in real life setting need to be considered	Need a validation

Abbreviations: CI, concordance index; C- statistic, concordance statistic; NPV, negative predictive value; PPV, positive predictive value; ECOG PS, Eastern Cooperative Oncology Group Performance Status.

Table 5 RAM in Haematological Malignancies; Cohort and Performance

RAM	Subtype	No	Performance
Leukaemia
KRS^Citation55	AML	867 AML	Suboptimal performance (P = 0.19)
ISTH-DIC^Citation8	AML/APL	272(adult)+ 132 (elderly) AML/63APL	Good performance, HR 4.79 (1.71–13.45)/ (P = 0.001).
AL Ani et al score	AML/APL/ALL	501	Good performance C-statistic of 0.664 (95% CI: 0.590–0.738)
Lymphoma
KRS^Citation31	Multiple validation studies		Unable stratify low risk patients
ThroLy score^Citation56,Citation57	All subtypes	1820 (derivation)+428(validation)	Inadequate discrimination
Hohaus el al. score^Citation58	All subtypes	857	Identified 82% of VTE but needs validation
TiC-Lympho^Citation59	All subtypes	254	AUC 0.783; however, a feasibility trial needed
CATSCORE^Citation18	All subtypes	249 in derivation	Needs validation
Multiple myeloma (MM)
IMPEDE VTE^Citation60 score	MM	Derivation 4446 Validation 4256	Good performance outperformed the current IMWG/NCCN guidelines (p < 0.0001)
SAVED Score^Citation61	MM	Derivation (2397) validation (1251)	Good performance (p < 0.01)
ROADMAP-CAT-MM score^Citation62	MM	144	Good performance, Feasibility validation trial required
KRS^Citation60	MM	2874	Poor prediction value c-statistic 0.52

Table 6 ISTH DIC Score

Variable	Value	Points
Platelet count	>100 x 109/L	0 Points
	>50 - <100 x 109/L	1 Points
	<50 x 109/L	2 Points
INR	<1.3	0 Points
	1.3–1.7	1 Points
	>1.7	2 Points
D-dimer	<400	0 Points
	400–4000	1 Points
	>4000	2 Points
Fibrinogen level	>1.0 g/L	0 Points
	<1.0 g/L	1 Point

Table 7 ThroLy Score

Patient Characteristics	Assigned Score
Previous VTE/acute myocardial infarction/stroke	2
Reduced mobility (ECOG 2‐4),	1
Obesity (BMI > 30 kg/m^2)	2
Extranodal localization	1
Mediastinal involvement	2
Neutrophils <1 × 10^9/L	1
Hemoglobin level <100 g/L	1

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