Therapeutic Significance of D-dimer Cut-off Level of more than 3 µg/ml in Colorectal Cancer...
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Therapeutic Significance of D-dimer Cut-off Level of more than 3 µg/ml in Colorectal Cancer Patients Treated with Standard Chemotherapy plus Bevacizumab DD Cut-off Level Sensitiv ity Specific ity ① 0.5 1.00 0.02 ② 1 1.00 0.11 ③ 1.5 1.00 0.38 ④ 2 0.75 0.49 ⑤ 2.5 0.75 0.62 ⑥ 3 0.75 0.72 ⑦ 3.5 0.50 0.75 ⑧ 4.0 0.50 0.77 ⑨ 4.5 0.50 0.82 ⑩ 5.0 0.50 0.83 ⑪ 5.5 0.50 0.88 ⑫ 6.0, 6.5, 7.0, 7.5 0.50 0.89 ⑬ 41 0.00 1.00 • A 70 years-old man with a recurrent rectal cancer after surgery, was treated with mFOLFOX6 *2) plus bev (5mg/kg qw2) for lung metastases. • Asymptomatic VTE was identified in the right internal jugular vein with the routinely enhanced CT scan on the day 439 after the initiation of bev, and anticoagulant therapy started immediately. • Two months later VTE was recovered, and mFOLFOX6 plus bev could restart with maintained anticoagulant therapy. • Sixty-nine pts with the total of 817 times of DD test performed were included between July 2007 and September 2008 at our institution. *1): lymph node *2): Oxaliplatin 85mg/m 2 , l-leucovorin 200mg/m 2 , 5- FU bolus 400mg/m 2 followed by infusional 5-FU 2400mg/m 2 46-hours qw 2 *3): CPT-11 150mg/m 2 , l-leucovorin 200mg/m 2 , 5-FU bolus 400mg/m 2 followed by infusional 5-FU 2400mg/m 2 46-hours qw 2 *4): l-leucovorin 250mg/m 2 , 5-FU bolus 500mg/m 2 qw *5): modified RECIST criteria version 1.1 *6): maximum DD level in each patient *7): positive predictive value *8): negative predictive value S.Mochizuki, T.Yoshino, T.Fukushima, N.Fuse, H.Ikematsu, K.Minashi, T. Yano, M.Tahara, K.Kaneko, T.Doi, A.Ohtsu Division of endoscopy and gastrointestinal oncology, National Cancer Center Hospital East, Kashiwa, Japan # A16 Updated Abstract Results Background Methods Patient Selection Criteria Patient Characteristics No. of pts 69 Gender: Male/Female 41/28 Age (yrs) : median (range) 63 (30-78) Primary side: right sided/left sided/ rectum 14/19/36 Metastatic site (overlaped) : liver/lung/peritoneum/LN *1) /ovary/bone 31/38/6/17/ 2/4 Concurrent regimen: mFOLFOX6 *2) /FOLFIRI *3) /5FU+l-LV *4) 43/25/1 1 st line chemotherapy / 2 nd line chemotherapy and over 45/24 Best Response *5) : CR/PR/SD/PD/NE 2/30/27/8/2 Treatment duration (mos) : median (range) 6 (1-18) No. of DD test per patient.: median (range) 10 (2-32) Baseline DD level (µg/ml) : median (range) 1.2 (0.2- 5.0) DD levels in VTE Cases Case Age Gender Primary site Concurrent regimen ＤＶ T site VTE onset Days after 1 st bev given DD level ( µg/ml) ① 70 M Rectum FOLFOX6+bev SVC 439 7.6 ② 49 M Rectum FOLFIRI+bev Left limb 219 7.9 ③ 74 M Sigmoid FOLFIRI+bev CV port 219 2.0 ④ 66 M Sigmoid FOLFOX6+bev CV port 42 3.3 day DD level (µg/ml) VTE References VTE Case ① 2 months later Conclusions Limitations Summary ROC analysis ① ② ③ ④ ⑤ ⑥ ⑦ ⑨ ⑧ ⑩ ⑫ ⑬ ⑪ DD Cut-off Level of > 1 µg/ml DD Cut-off Level of > 3 µg/ml Cases of D-dimer > 3 µg/ml • Out of the remnant 48 pts who showed DD levels kept to be < 3 µg/ml, 1 patient of VTE was identified. Objectives • The plasma measurement of D-dimer (DD) has been regarded as diagnostic aid in suspected venous thromboembolism (VTE) 1 . • Many cancer patients (pts) were reported to have elevated DD levels 2 . • Risk of VTE with bevacizumab (bev) in cancer patients were reported to be increasing 3 . • It is not clear which DD level might show the increased risk of VTE in the colorectal cancer (CRC) pts treated with standard chemotherapy plus bev. • The DD level of > 3 µg/ml might be an indicator of increased risk for VTE in CRC pts treated with standard chemotherapy plus bev. • Validation of the usefulness of the DD cut-off level of > 3 µg/ml is required, using the other large number of cohort. • 1. Bounameaux H, de Moerloose P, Perrier A, et al: Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 71:1-6, 1994 • 2. Nalluri SR, Chu D, Keresztes R, et al: Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300:2277-85, 2008 • 3. Yoshikawa R, Yanagi H, Noda M, et al: Venous thromboembolism in colorectal cancer patients with central venous • Median baseline DD level was 1.2 µg/ml (range 0.2-5.0). • The ROC analysis showed the DD cut-off level for the increased risk of VTE might be 3 µg/ml. • The sensitivity and specificity of the DD cut-off level of > 3 µg/ml were 75.0 percent and 72.3 percent, respectively. • Of the 48 pts who showed DD levels kept to be < 3 µg/ml, 1 patient of VTE was identified. • The relative risk of VTE incidence had a 6.9-fold increase among pts who showed elevated DD levels of > 3 µg/ml at any point during receiving bev. • Retrospective analysis. • Small sample size. • Selection bias. • Histologically proven metastatic and unresectable colorectal adenocarcinoma. • No prior chemotherapy containing bev. • DD test performed repetitively at the physicians’ preference on the baseline and during receiving bev. • No VTE identified at the baseline. • We retrospectively reviewed every DD level, whose upper limit of normal is 1 µg/ml measured with Latex Immuno Assay (LIA), and any event concurrent with elevated DD level including VTE and so on during all the clinical courses. • DD cut-off level was determined using ROC analysis with the maximum DD level in each patient. Background: The plasma measurement of D-dimer (DD) has been regarded as diagnostic aid in suspected venous thromboembolism (VTE). Risk of VTE with bevacizumab (bev) in cancer patients (pts) were reported to be increasing, and many cancer pts without VTE were reported to have elevated DD levels. It is not clear which DD level might show the increased risk of VTE in the colorectal cancer (CRC) pts treated with standard chemotherapy plus bev. This retrospective analysis was to determine the appropriate DD cut-off level for the increased risk of VTE in these CRC pts using Receiver Operating Characteristic (ROC) analysis. Methods: We reviewed every DD level, whose upper limit of normal is 1 µg/ml measured with Latex Immuno Assay (LIA), and any event concurrent with elevated DD level including VTE and so on during all the clinical courses. DD cut-off level was determined using ROC analysis with the maximum DD level in each patient. The selection criteria were: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bev; DD test performed repetitively at the physicians’ preference on the baseline and during receiving bev; No VTE identified at the baseline; enhanced chest and abdominal CT scan performed every 2 months basically to identify VTE and evaluate tumor progression. Results: Sixty-nine pts with the total of 817 times of DD test performed were included between July 2007 and September 2008 at our institution. The chemotherapy regimens with bev included FOLFOX (n=43), FOLFIRI (n=25) and 5-FU+l-LV (n=1). Median baseline DD level was 1.2 µg/ml (range 0.2-5.0). The ROC analysis showed the DD cut-off level for the increased risk of VTE might be 3 µg/ml. The sensitivity and specificity were 75 percent and 72 percent, respectively. Twenty-one of 69 (30.4 percent) pts showed elevated DD levels of > 3 µg/ml during receiving bev, which consisted of 10 pts of unknown reasons, 6 of tumor progression, 3 of VTEs, 1 of sepsis and 1 of tumor necrosis. Out of the remnant 48 pts who showed DD levels kept to be < 3 µg/ml, 1 patient of VTE was identified. The relative risk of VTE incidence had a 6.9-fold increase among pts who showed elevated DD levels of > 3 µg/ml at any point during receiving bev. • This retrospective analysis was to determine the appropriate DD cut-off level for the increased risk of VTE in these CRC pts using Receiver Operating Characteristic (ROC) analysis.
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Transcript of Therapeutic Significance of D-dimer Cut-off Level of more than 3 µg/ml in Colorectal Cancer...
Therapeutic Significance of D-dimer Cut-off Level of more than 3 µg/ml in Colorectal Cancer Patients Treated with Standard Chemotherapy plus Bevacizumab
DD Cut-off Level
Sensitivity
Specificity
① 0.5 1.00 0.02
② 1 1.00 0.11
③ 1.5 1.00 0.38
④ 2 0.75 0.49
⑤ 2.5 0.75 0.62
⑥ 3 0.75 0.72
⑦ 3.5 0.50 0.75
⑧ 4.0 0.50 0.77
⑨ 4.5 0.50 0.82
⑩ 5.0 0.50 0.83
⑪ 5.5 0.50 0.88
⑫ 6.0, 6.5, 7.0, 7.5
0.50 0.89
⑬ 41 0.00 1.00
• A 70 years-old man with a recurrent rectal cancer after surgery, was treated with mFOLFOX6*2) plus bev (5mg/kg qw2) for lung metastases.
• Asymptomatic VTE was identified in the right internal jugular vein with the routinely enhanced CT scan on the day 439 after the initiation of bev, and anticoagulant therapy started immediately.
• Two months later VTE was recovered, and mFOLFOX6 plus bev could restart with maintained anticoagulant therapy.
• Sixty-nine pts with the total of 817 times of DD test performed were included between July 2007 and September 2008 at our institution.
*1): lymph node
*2): Oxaliplatin 85mg/m2, l-leucovorin 200mg/m2, 5-FU bolus 400mg/m2 followed by infusional 5-FU 2400mg/m2 46-hours qw 2
*3): CPT-11 150mg/m2, l-leucovorin 200mg/m2, 5-FU bolus 400mg/m2 followed by infusional 5-FU 2400mg/m2 46-hours qw 2
*4): l-leucovorin 250mg/m2, 5-FU bolus 500mg/m2 qw
*5): modified RECIST criteria version 1.1*6): maximum DD level in each patient*7): positive predictive value*8): negative predictive value
S.Mochizuki, T.Yoshino, T.Fukushima, N.Fuse, H.Ikematsu, K.Minashi, T. Yano, M.Tahara, K.Kaneko, T.Doi, A.Ohtsu Division of endoscopy and gastrointestinal oncology, National Cancer Center Hospital East, Kashiwa, Japan
# A16
Updated Abstract ResultsBackground
Methods
Patient Selection Criteria
Patient Characteristics
No. of pts 69
Gender: Male/Female 41/28
Age (yrs) : median (range) 63 (30-78)
Primary side: right sided/left sided/ rectum 14/19/36
Metastatic site (overlaped) :
liver/lung/peritoneum/LN*1)/ovary/bone 31/38/6/17/2/4
Concurrent regimen: mFOLFOX6*2)/FOLFIRI*3)/5FU+l-LV*4)
43/25/1
1st line chemotherapy / 2nd line chemotherapy and over 45/24
Best Response*5): CR/PR/SD/PD/NE 2/30/27/8/2
Treatment duration (mos) : median (range) 6 (1-18)
No. of DD test per patient.: median (range) 10 (2-32)
Baseline DD level (µg/ml) : median (range) 1.2 (0.2-5.0)
DD levels in VTE Cases
Case Age GenderPrimary
siteConcurrent
regimenＤＶ T
site
VTE onset
Days after 1st bev given
DD level ( µg/ml)
① 70 M Rectum FOLFOX6+bev SVC 439 7.6
② 49 M Rectum FOLFIRI+bev Left limb 219 7.9
③ 74 M Sigmoid FOLFIRI+bev CV port 219 2.0
④ 66 M Sigmoid FOLFOX6+bev CV port 42 3.3
day
DD level (µg/ml)
VTE
References
VTE Case ①
2 months later
Conclusions
Limitations
Summary
ROC analysis① ② ③
④ ⑤ ⑥
⑦⑨
⑧
⑩⑫
⑬
⑪
DD Cut-off Level of > 1 µg/ml DD Cut-off Level of > 3 µg/ml
Cases of D-dimer > 3 µg/ml
• Out of the remnant 48 pts who showed DD levels kept to be <3 µg/ml, 1 patient of VTE was identified.
Objectives
• The plasma measurement of D-dimer (DD) has been regarded as diagnostic aid in suspected venous thromboembolism (VTE) 1.
• Many cancer patients (pts) were reported to have elevated DD levels 2.
• Risk of VTE with bevacizumab (bev) in cancer patients were reported to be increasing 3.
• It is not clear which DD level might show the increased risk of VTE in the colorectal cancer (CRC) pts treated with standard chemotherapy plus bev.
• The DD level of > 3 µg/ml might be an indicator of increased risk for VTE in CRC pts treated with standard chemotherapy plus bev.
• Validation of the usefulness of the DD cut-off level of > 3 µg/ml is required, using the other large number of cohort.
• 1. Bounameaux H, de Moerloose P, Perrier A, et al: Plasma measurement of D-dimer as diagnostic aid in suspected venous thromboembolism: an overview. Thromb Haemost 71:1-6, 1994
• 2. Nalluri SR, Chu D, Keresztes R, et al: Risk of venous thromboembolism with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis. JAMA 300:2277-85, 2008
• 3. Yoshikawa R, Yanagi H, Noda M, et al: Venous thromboembolism in colorectal cancer patients with central venous catheters for 5-FU infusion-based pharmacokinetic modulating chemotherapy. Oncol Rep 13:627-32, 2005
• Median baseline DD level was 1.2 µg/ml (range 0.2-5.0).
• The ROC analysis showed the DD cut-off level for the increased risk of VTE might be 3 µg/ml.
• The sensitivity and specificity of the DD cut-off level of > 3 µg/ml were 75.0 percent and 72.3 percent, respectively.
• Of the 48 pts who showed DD levels kept to be < 3 µg/ml, 1 patient of VTE was identified.
• The relative risk of VTE incidence had a 6.9-fold increase among pts who showed elevated DD levels of > 3 µg/ml at any point during receiving bev.
• Retrospective analysis.• Small sample size.• Selection bias.
• Histologically proven metastatic and unresectable colorectal adenocarcinoma.
• No prior chemotherapy containing bev.
• DD test performed repetitively at the physicians’ preference on the baseline and during receiving bev.
• No VTE identified at the baseline.
• Enhanced chest and abdominal CT scan performed every 2 months basically to identify VTE and evaluate tumor progression.
• We retrospectively reviewed every DD level, whose upper limit of normal is 1 µg/ml measured with Latex Immuno Assay (LIA), and any event concurrent with elevated DD level including VTE and so on during all the clinical courses.
• DD cut-off level was determined using ROC analysis with the maximum DD level in each patient.
Background: The plasma measurement of D-dimer (DD) has been regarded as diagnostic aid in suspected venous thromboembolism (VTE). Risk of VTE with bevacizumab (bev) in cancer patients (pts) were reported to be increasing, and many cancer pts without VTE were reported to have elevated DD levels. It is not clear which DD level might show the increased risk of VTE in the colorectal cancer (CRC) pts treated with standard chemotherapy plus bev. This retrospective analysis was to determine the appropriate DD cut-off level for the increased risk of VTE in these CRC pts using Receiver Operating Characteristic (ROC) analysis.
Methods: We reviewed every DD level, whose upper limit of normal is 1 µg/ml measured with Latex Immuno Assay (LIA), and any event concurrent with elevated DD level including VTE and so on during all the clinical courses. DD cut-off level was determined using ROC analysis with the maximum DD level in each patient. The selection criteria were: histologically proven metastatic and unresectable colorectal adenocarcinoma; no prior chemotherapy containing bev; DD test performed repetitively at the physicians’ preference on the baseline and during receiving bev; No VTE identified at the baseline; enhanced chest and abdominal CT scan performed every 2 months basically to identify VTE and evaluate tumor progression.
Results: Sixty-nine pts with the total of 817 times of DD test performed were included between July 2007 and September 2008 at our institution. The chemotherapy regimens with bev included FOLFOX (n=43), FOLFIRI (n=25) and 5-FU+l-LV (n=1). Median baseline DD level was 1.2 µg/ml (range 0.2-5.0). The ROC analysis showed the DD cut-off level for the increased risk of VTE might be 3 µg/ml. The sensitivity and specificity were 75 percent and 72 percent, respectively. Twenty-one of 69 (30.4 percent) pts showed elevated DD levels of > 3 µg/ml during receiving bev, which consisted of 10 pts of unknown reasons, 6 of tumor progression, 3 of VTEs, 1 of sepsis and 1 of tumor necrosis. Out of the remnant 48 pts who showed DD levels kept to be < 3 µg/ml, 1 patient of VTE was identified. The relative risk of VTE incidence had a 6.9-fold increase among pts who showed elevated DD levels of > 3 µg/ml at any point during receiving bev.
Conclusions: The DD level of > 3 µg/ml might be an indicator of increased risk for VTE in CRC pts treated with standard chemotherapy plus bev. Validation of the usefulness of the DD cut-off level of > 3 µg/ml is required, using the other large number of cohort.
• This retrospective analysis was to determine the appropriate DD cut-off level for the increased risk of VTE in these CRC pts using Receiver Operating Characteristic (ROC) analysis.
