dose escalation of low molecular weight heparin to manage
ORIGINAL ARTICLE
Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients
M.C A R R I E R,* G.L E G A L,àR.C H O,§S.T I E R N E Y,* M.R O D G E R* and A.Y.L E E–
*Thrombosis Program,Division of Hematology,Department of Medicine,University of Ottawa,Ottawa,ON; Clinical Epidemiology Program, The Ottawa Health Research Institute,Ottawa,ON;àDepartment of Internal Medicine and Chest Diseases,EA3878,Brest University Hospital, Brest,France;§Department of Medicine,Michael G.DeGroote School of Medicine,McMaster University,Hamilton,ON;and–Thrombosis Program,Department of Medicine,University of British Columbia,Vancouver,BC and Department of Medicine,McMaster University,Hamilton, ON,Canada
To cite this article:Carrier M,Le Gal G,Cho R,Tierney S,Rodger M,Lee AY.Dose escalation of low molecular weight heparin to manage recurrent venous thromboembolic events despite systemic anticoagulation in cancer patients.J Thromb Haemost2009;7:760à5.
Summary.Background:Cancer patients with venous throm-boembolism(VTE)are at high risk of recurrent VTE despite standard anticoagulation.To date,very little published literature is available to guide the treatment of cancer patients with recurrent VTE.Objectives:To evaluate the bene?t and risk of low molecular weight heparin(LMWH) dose escalation in cancer patients with recurrent VTE. Patients and methods:This was a retrospective cohort study of consecutive cancer outpatients referred for management of a symptomatic,recurrent VTE while receiving an anticoag-ulant.Con?rmed episodes of recurrent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH,or initiation of therapeutic dose LMWH in patients who were taking a vitamin K antagonist (VKA).All patients were followed for a minimum of 3months after the index recurrent VTE unless they died during this period.Results:Seventy cancer patients with a recurrent VTE despite ongoing anticoagulation were included.At the time of the recurrence,67%of patients were receiving LMWH,and33%were receiving a VKA.A total of six patients[8.6%;95%con?dence interval (CI)4.0à17.5%]had a second recurrent VTE during the 3-month follow-up period,at an event rate of9.9per 100patient-years(95%CI 2.0à17.8%).Three patients (4.3%;95%CI 1.5à11.9%),or 4.8per100patient-years (95%CI0.0à10.3%)of follow-up,had bleeding complica-tions.The median time between the index recurrent VTE to death was11.4months(range,0à83.9months).Conclusions: Cancer patients with recurrent VTE have a short median survival.Escalating the dose of LMWH can be e?ective for treating cases that are resistant to standard,weight-adjusted doses of LMWH or a VKA.
Keywords:cancer,cancer-associated thrombosis,low molecular weight heparin,recurrent venous thromboembolism, treatment.
Background
Patients with cancer have a four-fold increased risk of developing a venous thromboembolism(VTE)relative to the general population[1,2].They also have a three-fold risk of recurrent VTE and a three-fold to six-fold risk of major bleeding while receiving anticoagulant treatment with a vita-min K antagonist(VKA),as compared with patients without cancer[3à5].Low molecular weight heparin(LMWH)therapy for3à6months is now recommended over VKA as a?rst-line treatment to reduce the risk of recurrent VTE in patients with active cancer[6,7],on the basis of several randomized controlled trials that compared the relative ef?cacy and safety of LMWH with VKA therapy[8,9].In the CLOT trial,a therapeutic dose of dalteparin for the?rst month followed by a ?maintenance?dose of75à80%of the full therapeutic dose for the next5months reduced the relative risk of recurrent VTE in the dalteparin group by52%[8].Importantly,differences in bleeding and survival were not observed.
The CLOT study also demonstrated that9à17%of cancer patients will develop recurrent VTE,despite therapy with LMWH or VKA,over6months of follow-up.Furthermore, the overall survival of these patients was reduced:60%were dead within1year after the diagnosis of VTE.To date,very little published literature is available to guide the treatment of
Correspondence:Agnes Y.Lee,Director of Thrombosis,Division of
Hematology,University of British Columbia,Diamond Health Care
Center,2775Laurel Street10th?oor,Vancouver,BC,V5Z1M9,
Canada.
Tel.:+16048754952;fax:+16048754696.
E-mail:alee14@bccancer.bc.ca
Received20November2008,accepted11February2009
Journal of Thrombosis and Haemostasis,7:760à765DOI:10.1111/j.1538-7836.2009.03326.x
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cancer patients with recurrent VTE despite standard anti-coagulation treatment.
The American College of Chest Physicians previously recommended the insertion of an inferior vena cava(IVC)?lter in patients with recurrent VTE while on anticoagulant therapy[10].However,this recommendation has been withdrawn from the most recent guidelines published in June2008[7].For cancer patients with recurrent VTE,the American Society of Clinical Oncology recommends the use of an alternate anticoagulant regimen(e.g.switch to LMWH if the patient had been receiving a VKA),or the insertion of an IVC?lter,as a possible management option [6].However,these recommendations are based on weak evidence.Indeed,the risk of recurrent deep vein thrombosis (DVT)after IVC?lter insertion has been reported to be as high as32%in patients with cancer,and is associated with signi?cant morbidity and poor quality of life[5,11à14]. These poor outcomes are not unexpected,as?lters do not control or dampen the hypercoagulable state in these patients,and may introduce another nidus for thrombus formation.
Dose escalation of LMWH may represent an alternative to IVC?lter insertion in cancer patients with recurrent VTE.A retrospective study of32patients suggested that LMWH therapy might be effective in the management of recurrent VTE in patients taking a VKA[15].In that particular study,63%of patients had a diagnosis of cancer.It is currently unknown whether dose escalation of LMWH would be effective and safe for treating recurrent VTE in cancer patients already on LMWH.One case report has described successful management of recurrent VTE in a patient with cervical cancer using a supratherapeutic dose of LMWH[16].
To further evaluate the bene?t and risk of LMWH dose escalation in cancer patients with recurrent VTE,we performed a retrospective study in two large thrombosis clinics. Patients and methods
Patient population
A retrospective cohort study of consecutive cancer outpa-tients referred for management of a symptomatic,recurrent VTE while receiving an anticoagulant was conducted at the Ottawa Hospital Thrombosis Unit,Ottawa,ON(July2004 to June2008;n=31)and the Henderson Hospital Outpa-tient Thrombosis Unit,Hamilton,ON(April2003to June 2007;n=39).Patients were included if they had:(i) documented active malignancy;(ii)objectively proven?rst episode of VTE[proximal lower extremity DVT,upper extremity DVT or pulmonary embolism(PE)];and(iii) objectively documented recurrent VTE(either new or extended proximal lower extremity DVT,upper extremity DVT,or PE)while taking systemic anticoagulation medica-tion(LMWH or a VKA).Only cases with symptomatic VTE were included.Research ethics board approval was obtained for the study.
Data collection
The following variables were prespeci?ed prior to data collection:(i)patient demographics;(ii)management of the initial VTE;(iii)cancer history(site and stage);(iv)dates of diagnosis of the initial and recurrent episodes of VTE;(v) radiologic evidence of the location/extent of the initial and recurrent VTE;(vi)dose of LMWH(therapeutic,maintenance, low dose)or International Normalized Ratio(INR)(thera-peutic or subtherapeutic)at the time of the index recurrent VTE;(vii)management of the index recurrent VTE;(viii) further recurrent VTE or bleeding within3months after the index recurrence;and(ix)death(date and cause).Other information relevant to recurrent VTE or bleeding events,such as withholding of anticoagulation treatment for surgery,was also recorded.
For this study,a therapeutic dose of LMWH was de?ned as dalteparin200units kg)1once daily,tinzaparin175units kg)1 once daily,or enoxaparin1mg kg)1twice daily or1.5mg kg)1 once daily.The maintenance dose of LMWH was de?ned as 75à80%of the full therapeutic dose.Low dose was de?ned as any dose less than75%of the full therapeutic dose.The therapeutic anticoagulation for VKA was de?ned as an INR greater than or equal to2.0.Subtherapeutic INR was de?ned as less than2.0.
Data were extracted independently by two investigators at each site.Disagreements on information were resolved by consensus or retrieving further information from other medical records.
Management
The management of recurrent VTE was consistent at both thrombosis units.All objectively con?rmed episodes of recur-rent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH or initiation of a therapeutic dose of LMWH in patients who were taking a VKA.Patients on a therapeutic dose of LMWH at the time of the recurrent VTE were managed by increasing the weight-adjusted dose by20à25%for at least4weeks.Patients on a maintenance dose were treated by increasing the LMWH to a therapeutic dose for6à12weeks.Patients on low-dose LMWH were managed by increasing the LMWH to a therapeutic dose for1month,and using a maintenance dose thereafter.Similarly,patients on a VKA(therapeutic or subtherapeutic)were treated with a therapeutic dose of LMWH for1month,followed by a maintenance dose.Anti-factor Xa measurements at the time of the index recurrent VTE or after dose escalation were not routinely performed. Outcome assessment and follow-up
All patients were followed for a minimum of3months after the index recurrent VTE,unless they died during this period.The primary outcome measure was the incidence of a second, symptomatic recurrent VTE diagnosed over a3-month Recurrent venous thromboembolism in patients with cancer761
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follow-up period after the?rst(index)recurrent VTE.Initial proximal lower extremity DVT was de?ned a non-compressible segment on compression leg vein ultrasound imaging in the popliteal vein or a more proximal leg vein.Initial upper extremity DVT was de?ned as a non-compressible segment on compression ultrasound in the brachial or internal jugular deep veins,or absent?ow in the subclavian vein.Initial PE was de?ned as a high-probability ventilation/perfusion(V/Q)lung scan or a segmental or larger pulmonary artery?lling defect on spiral computed tomography(sCT)scan.Recurrent DVT was de?ned as a new non-compressible site or proximal extension from a previous measurement.Recurrent PE was de?ned as a new mismatched segmental or greater perfusion defect on V/Q scan or a new intraluminal?lling defect in a segmental or larger pulmonary artery on sCT scan.
Secondary outcome measures included minor and major bleeding over the3-month period after the index recurrent VTE (regardless of the status of anticoagulation at the time of the bleed),and overall and VTE-related death.Major bleeding events were de?ned as:(i)fatal bleeding;(ii)symptomatic bleeding in a critical area or organ,such as intracranial, intraspinal,intraocular,retroperitoneal,intra-articular or peri-cardial,or intramuscular with compartment syndrome;and(iii) bleeding causing a fall in hemoglobin level of20g L)1or more, or leading to transfusion of two or more units of whole blood or red cells[17].Date of last follow-up and date of death(if available in the clinic chart)were recorded.VTE-related death was de?ned as a fatal PE con?rmed on autopsy or as an unexplained sudden death[18].
Analyses
A descriptive summary of the baseline characteristics of the cohort is provided.We reported the proportions,with95% con?dence intervals(CIs),of patients with a second or more episodes of recurrent VTE and major bleeding during the 3-month follow-up period.The corresponding event rates were calculated on the basis of100patient-years of follow-up.A KaplanàMeier survival curve was constructed to estimate the time to the index recurrent VTE from the initial diagnosis,and a separate curve was plotted to estimate overall survival following the index recurrent VTE.Patients were censored after the last known date of follow-up or death.The median time between the initial and index recurrent VTE,and the median time between the index recurrent VTE and death,were determined. Results
Seventy cancer patients with a recurrent VTE despite ongoing anticoagulation are included in this report.The study partic-ipants?characteristics are summarized in Table1.The median age was60years(range,27à84years).Thirty-eight(54%) were female.Forty-four patients(63%)had metastatic cancer at the time of their initial VTE.The most common type of cancer was lung carcinoma.At the time of the initial VTE,39 patients(56%)had a proximal lower extremity DVT,12(17%)had an upper extremity DVT(?ve cases were catheter-related), 14(20%)had a PE,and?ve(7%)had both a leg DVT and a PE.
At the time of the symptomatic index recurrence,47(67%) patients were on LMWH,and23(33%)were on VKAs.Of the 47patients on LMWH,15(32%),24(51%)and eight(17%) were on therapeutic,maintenance and low doses,respectively. Eleven(48%)and seven(30%)of the23patients on VKAs had a therapeutic(?2)and subtherapeutic INR,respectively, whereas?ve(22%)patients did not have a documented INR result at the time of the recurrent VTE event.
Of the70index recurrent VTEs,40(57%)involved the lower extremity,13(19%)occurred in an upper extremity(?ve were catheter-related),and15(21%)presented as PE.Two(3%) patients had a recurrent VTE in the IVC.Table2summarizes the location and extent of the index recurrences.It is of note that67%of the recurrent VTEs developed at a new site(e.g. the initial episode was a right leg DVT,and the recurrent episode presented as a PE).The median time between the initial VTE to recurrence(index episode)was3.5months(range, 0.3à193months)(Fig.1).A total of20patients(29%)had the index recurrent VTE less than4weeks following the initial diagnosis.
All70objectively con?rmed episodes of recurrent VTE were treated with either dose escalation of LMWH in patients already anticoagulated with LMWH or initiation of therapeu-tic-dose LMWH in patients who were taking a VKA.Three patients also had an IVC?lter inserted.Overall,55patients were treated with a therapeutic dose of LMWH,and15 patients received120%of a therapeutic dose of LMWH for the index recurrent VTE.
A total of six patients(8.6%;95%CI 4.0à17.5%)had a second recurrent VTE during the3-month follow-up period,at an event rate of9.9per100patient-years(95%CI 2.0à17.8%).The median time between the index and second recurrent VTE was1.9months(range,0.6à3.0months).Three patients(50%)had their second recurrence while on therapeu-tic doses of LMWH,and the other three were on120%of a therapeutic dose of LMWH.All were treated by increasing the weight-adjusted dose by20à25%for at least4weeks,and one patient had an IVC?lter inserted as well.None of these patients had any further recurrent thrombotic event during the 3-month follow-up period.Of these six patients with a second recurrence,?ve(83%)had metastatic disease and four(67%) had an underlying diagnosis of lung carcinoma.
Only three patients(4.3%;95%CI 1.5à11.9%),or4.8per 100patient-years(95%CI0.0à10.3%)of follow-up,had bleeding complications after their index recurrent VTE.One patient with a malignant brain tumor had an intracranial bleed after the LMWH was increased to a therapeutic dose.Two patients(2.9%;95%CI0.9à9.8%)had a minor bleeding episode while receiving therapeutic LMWH.
At the time of the last follow-up,a total of36patients were dead.None of the deaths were related to the recurrent VTE or bleeding.The median time between the index recurrent VTE to death was11.4months(range,0à83.9months)(Fig.2).The
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median survival was only 4.3months (range,0.9à4.9months)after a second recurrence (data not shown).Discussion
This is the largest report on the management and outcomes of cancer patients following a recurrent episode of VTE while they were being treated with an anticoagulant.Our retrospective cohort study demonstrates that recurrent VTE in cancer patients can be effectively and safely managed by escalating the dose of LMWH or switching to LMWH from warfarin.Although the exact dosing of LMWH for the recurrent VTE differed (depending on the anticoagulant regimen at the time of the recurrence),escalating the dose of LMWH resulted in a second recurrent VTE rate of 8.6%(95%CI 4.0à17.5%),and it was well tolerated,with few bleeding complications.The high rate of response to dose escalation suggests that recurrent VTE in cancer patients might be a consequence of ?resistance ?to standard doses of LMWH,and that higher doses are needed.This is in contrast to a true failure of LMWH anticoagulation,whereby dose escalation is not successful and other therapeutic
Table 1Baseline characteristics
LMWH
(N =47)(n ,%)
Vitamin K antagonist
(N =23)(n ,%)Study population (N =70)(n ,%;95%CI)
Female
25(53.2)13(56.5)38(54.3;42.7à65.5)Age,years (median;range)58(27à83)64(49à90)60(27à90)Cancer location Lung 15(31.9)6(26.1)21(30.0;20.5à41.6)Colon 9(19.2)1(4.3)10(14.3;8.0à24.4)Breast 3(6.3)2(8.6)5(7.1;3.2à15.7)GI 10(21.3)2(8.6)12(17.1;10.1à27.7)GU
1(2.1)3(13.0)4(5.7;2.3à13.8)Gynecological 2(4.3)3(13.0)5(7.1;3.2à15.7)Hematological 4(8.5)2(8.6)6(8.6;4.1à17.5)Other
3(6.3)
4(17.4)
7
(10.0;5.0à19.3)
Cancer stage
Non-metastatic 18(38.3)6(26.1)24(34.3;24.2à46.0)Metastatic 28(59.6)16(69.6)44(62.9;51.1à73.2)NA
1(2.1)1(4.3)2(2.9;0.9à9.8)Initial VTE
Lower extremity DVT 24(51.1)15(65.2)39(55.7;44.0à66.8)Upper extremity DVT 9(19.2)3(13.0)12(17.1;10.1à27.7)Catheter-related 5(10.6)05(7.1;3.2à15.7)PE
11(23.4)3(13.0)14(20.0;12.3à30.9)DVT and PE
3(6.3)
2(8.6)
5
(7.1;3.2à15.7)
Anticoagulation at time of recurrence (n ,%;95%CI)(n ,%;95%CI)LMWH
Therapeutic dose 15(21.4;13.5à32.4)NA Maintenance dose 24(34.3;24.2à46.0)NA Low dose
8(11.4;6.0à21.0)NA
Vitamin K antagonists Therapeutic NA 11(15.7;9.1à26.0)Subtherapeutic NA 8(11.4;6.0à21.0)Unknown
NA
4(5.7;2.3à13.8)
CI,con?dence interval;DVT,deep vein thrombosis;GI,gastrointestinal;GU,genitourinary;LMWH,low molecular weight heparin;NA,not applicable;PE,pulmonary embolism;VTE,venous thromboembolism.
Table 2Recurrent venous thromboembolism events
Study population (N =70)
Recurrent lower extremity DVT (n ,%;95%CI)40(57.4;45.4à68.1)Ipsilateral
13(18.6;11.2à29.3)Ipsilateral and new upper extremity DVT 1(1.4;0.3à7.6)Contralateral 12(17.1;10.1à27.7)Bilateral 3(4.3;1.6à11.9)New DVT
11(15.7;9.1à26.0)Recurrent upper extremity DVT (n ,%;95%CI)13(18.6;11.2à29.3)Ipsilateral 3(4.3;1.6à11.9)Contralateral
1(1.4;0.3à7.6)New upper extremity DVT 9(12.9;7.0à22.7)Recurrent PE (n ,%;95%CI)15(21.4;13.5à32.4)Recurrent PE 7(10.0;5.0à19.3)New PE
8(11.4;6.0à21.0)Other (IVC thrombus)(n ,%;95%CI)
2
(2.9;0.9à9.8)
CI,con?dence interval;DVT,deep vein thrombosis;PE,pulmonary embolism;IVC,inferior vena cava.
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options would be required to suppress the hypercoagulable state.The heightened hypercoagulable state in these patients is also indirectly re?ected by the short time to recurrence:29%of the index recurrences occurred within the ?rst 4weeks of treatment.We can only speculate on the mechanism of anticoagulant resistance.Given that the majority of patients responded to a higher dose of LMWH,it is likely that these patients did not achieve therapeutic levels with standard,weight-adjusted doses of LMWH.Whether this is due to lower bioavailability from increased non-speci?c binding of LMWH to plasma proteins or cells,enhanced renal clearance,or perhaps a large clot burden,is unknown.We were unable to explore these hypotheses,because of the retrospective design of the study and the lack of anti-FXa levels at the time of the recurrence.
Our study also shows that the median survival of patients
with recurrent VTE,especially following a second recurrent VTE,is very poor in cancer patients.Previous studies have demonstrated that cancer patients who develop a VTE have a shorter life expectancy than matched cohorts without thrombotic complications [19à21].The short median survival of 11.4months after a recurrent VTE in our study is consistent with a previously published report of a small cohort of cancer patients with recurrent VTE [22].It is unknown whether the early deaths are due to undiagnosed fatal PE or aggressive malignancies,which may have contributed to the anticoagulant resistance or failure.This should be taken into consideration when managing cancer patients with recurrent VTE.
There are limitations of our study.First,this is a retrospec-tive cohort study,and the results may be subject to bias,incomplete information,or misdiagnosis.We tried to minimize selection bias by including all consecutive patients assessed at the two different thrombosis units.Charts of all patients with a diagnosis of cancer were fully reviewed by two reviewers independently,to identify patients with recurrent VTE on anticoagulants,and only patients with objectively diagnosed,symptomatic events were included.Second,a control group of cancer patients without a recent VTE were not available for comparison to evaluate the impact on survival or risk factors for recurrent VTE.Third,anti-FXa measurements were not routinely performed at the time of the index recurrent VTE.This is dif?cult to do in practice,as patients do not present at a time when peak or trough levels can be taken.Also,previous studies have shown a poor correlation between anti-FXa levels and clinical outcome [23,24].Fourth,the total numbers of second recurrent VTEs and bleeding events were https://www.wendangku.net/doc/4a11811004.html,rger studies are needed to provide more reliable estimates of the risk of recurrent VTE,bleeding and overall survival after dose escalation with LMWH.Conclusion
Cancer patients with recurrent VTE have a poor prognosis.Although the evidence is limited,our study suggests that escalating the dose of LMWH can be effective for treating cases that are resistant to standard,weight-adjusted doses of LMWH or a VKA.Prospective trials are required to assess the effectiveness and safety of this management option and to identify those who are at highest risk of anticoagulant resistance.
Disclosure of Con?ict of Interests
The authors state that they have no con?ict of interest.References
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12243648607284
Number
at risk
7011
8
22
2
1
Time (months)0.0
0.2
0.4
0.6
0.8
1.0
P r o p o r t i o n o f p a t i e n t s f r e e o f r e c u r
r e n t V T E Time to recurrrent VTE
Fig.1.Time to index recurrent venous thromboembolism (VTE)after
initial diagnosis of VTE.
Number at risk
70
20
103
211
Tiime (months)0
1224
3648607284
0.0
0.2
0.4
0.6
0.81.0
C u m u l a t i v e s u r v i v a l
Survival after recurrent VTE in cancer patients Fig.2.Kaplan àMeier survival curve after index recurrent venous thromboembolism (VTE).
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Recurrent venous thromboembolism in patients with cancer765
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医科达直线加速器真空系统维保探讨
医科达直线加速器真空系统维保探讨 摘要直线加速器是目前主流的放疗设备，它们的正常运行离不开真空技术，真空技术在直线加速器中的作用主要有：①避免加速管内放电击穿；②防止电子枪阴极中毒、钨丝材料的热子或灯丝氧化，③减少电子与加速管内气体的碰撞损失。既然真空系统如此重要，在我们日常的维保中我们该如何做才能保证真空系统正常有效运行呢？本文根据多年的维保经验做一个总结，希望可以为医院同行加速器真空维保时做一个参考。 关键词真空系统；加速器；钛泵 1 医用直线加速器的核心部件真空系统分类 （1）全密封驻波加速管。这种加速管真空度超高，真空度在10-7Torr以上，配一台小离子泵（3-5L/S）维持超高真空度，主要在一些低能的加速器中应用。 （2）具有可拆卸密封的驻波加速管。一些高能的驻波加速管，考虑到某些寿命件的可更换性，如电子枪阴极的更换，配置一台大的离子泵（20L/S），同时在电子枪部位增加一台较小的离子泵（8L/S），真空度在10-6-10-7Torr之间，Varian 高能加速器采取这种模式。 （3）具有可拆卸密封的行波加速管。将加速管设计成可拆卸式金属密封，一旦如电子枪、偏转靶室、离子泵等发生问题，可在医院现场更换，因行波加速管体积较大，一般配置一台大的离子泵（20-30L/S），分别装在两个耦合器的波导三通上，真空度在10-6Torr以上，Elekta加速器采取这种模式，本文重点讨论这种真空系统的维保[1]。 2 Elekta加速器真空系统构成 ①分子泵②钛泵及电源③真空监测单元④管路阀门组件等。 真空建立过程： （1）摘掉枪灯丝供电端子，用分子泵抽12小时左右建立10-4Torr左右的真空度。 （2）关闭截止阀，启动钛泵电源，让钛泵进一步提升真空度，在此过程中一定要密切注意钛泵的温度。 （3）待真空达到10-5Torr以上，控制台真空度参数达到5.5左右时，加枪灯丝电源，此时真空有一个下降再缓慢上升的过程。 （4）待控制台真空度参数稳定在5.7左右时，采用100MU的剂量率开始出
医科达电子直线加速器技术参数(上海
医科达电子直线加速器技术参数 1、双模式的数字化加速器，提供宽范围的X线和电子线能量，充分满足放射治疗外照射的临床需要。 2、射线束能量：多能量可定制性：多至2档X射线能量(4~18MV)和6档电子线能量(4~20MeV) 3、主机性能及配置： （1）独特设计的滚筒式机架：高度可靠性和稳定性，开放的机架结构，便于维修，最低的等中心高度（124cm），最大的等中心到治疗头的净空间距离45cm。 （2）高效能的行波加速管：行波加速管二十年无条件保用，允许较低的电压梯度，对行波加速管的真空要求低，使电子枪等部件可快速拆卸并易于更换。 （3）大功率FasTraQ磁控管：专门的紧凑型微波功率源，5MW功率输出，具有快速调谐的能力，快速的束流切换特性<0.1秒，提供24个月的保用期。 （4）滑雪式偏转系统：完全的消色散系统，并维持射束的对称性，伺服控制的三极磁偏转系统，精确的靶点聚焦，极佳的半影。（5）可单独拆卸更换灯丝的电子枪：电子枪伺服系统反应快速，确保束流能量的精度。
（6）六通道开放式结构的电离室：最新型超薄壁陶瓷材料电离室，自动校正KTP（温度、湿度、气压），监测射线的剂量、对称性和平坦度，具有长期的高灵敏和高稳定性，适合精确的伺服控制射线束流，重复精度：+/-0.5%，线性精度：+/-1%，2-10MU时的线性精度对保证IMRT的放疗精度尤其重要，旋转（运动束流）投照时的稳定性：±1%，分辨率：0.1MU。 （7）运动系统：用于操纵治疗头、机架及病人床的运动，手控盒可操纵加速器的所有动作，治疗头上有四个控制钮，可操纵治疗头的所有运动，治疗床两边各有一个控制板，可操纵床的所有运动，所有运动都是无线调速。 （8）安全连锁系统：通过硬件限位和软件防碰撞二种方式，确保病人和操作人员的安全。 （9）真空系统：维持加速管和电子枪的真空状态，在加速器中有效使用离子泵，有助于减少能源消耗，保护环境，并维持高的开机率。（10）水冷系统（内循环）：保证加速器的频率稳定，进而保证能量的稳定，用于加速器的热交换。 4、控制系统：全新的第三代全集成、全数字控制系统，确保更为平顺的流程工作方式，有效地提高治疗病人的周转率，基于Windows 平台的图形用户界面，易学习和使用，模块化软件结构，配置安装各
医科达直线加速器参数
Precise全数字直线加速器 双模式的数字化加速器，提供宽围的X线和电子线能量，充分满足放射治疗外照射的临床需要。 具有如下详述的特征和配置： 1.0 射线束能量 Precise数字化加速器具有无可匹敌的多能量可定制性：2档X射线能量（4~15MV）和9档电子线能量（4~22MeV） 2.0 Precise全数字直线加速器主机系统包含如下特性： 独特设计的滚筒式机架直线加速器 -由强劲的刚性结构带来的高度可靠性和稳定性 -开放的机架结构，便于维修，需维护的重要部件均分布在易于接近的位置 -最低的等中心高度（124cm），具有最优的临床可用性 -最大的等中心到治疗头的净空间距离45cm 高效能的行波加速管 -行波加速管二十年无条件保用 -允许较低的电压梯度，对行波加速管的真空要求低，使电子枪等部件可快速拆卸并易于更换 大功率FasTraQ磁控管： -专门的紧凑型微波功率源，5MW功率输出，具有快速调谐的能力 -快速的束流切换特性<0.1秒 -提供24个月的保用期 独有的滑雪式偏转系统： -完全的消色散系统，并维持射束的对称性 -伺服控制的三极磁偏转系统 -精确的靶点聚焦，极佳的半影 可单独拆卸更换灯丝的电子枪 -电子枪伺服系统反应快速，确保束流能量的精度 -易于更换，维护费用低 六通道开放式结构的电离室 -最新型超薄壁瓷材料电离室 -自动校正KTP（温度、湿度、气压），监测射线的剂量、对称性和平坦度 -具有长期的高灵敏和高稳定性，适合精确的伺服控制射线束流 -重复精度：+/-0.5% -线性精度：+/-1% -2-10MU时的线性精度对保证IMRT的放疗精度尤其重要 -旋转（运动束流）投照时的稳定性：±1% -分辨率：0.1MU 运动系统 -用于操纵治疗头、机架及病人床的运动 -手控盒可操纵加速器的所有动作
加速器相关英语缩略语定义(医科达)
加速器缩略语定义Abbreviation Definition ABCActive BreathingCoordinator主动呼吸协调器 ACBarm control board 臂控制板 AFCautomatic frequencycontrol 自动频率控制 AFDaxis filmdistance 轴向膜距 AIangiographicimage血管造影图像 ALARPas low as reasonablepracticable尽可能低 AmSiAmorphousSilicon 非晶硅 APSAutomatic PositioningSystem?自动定位系统? ASUassisted setup辅助设置 BCBendingCoarse弯曲粗 BEVbeam eyeview光束视角 BFBendingFine弯曲细度 BLDbeam limitingdevice限束装置 BLSbeam limitingsystem束流限制系统 BMPBitmap (imageformat)位图(图像格式) BOMbill ofmaterials材料单 CANcontroller area network控制器局域网 CATcustomer acceptancetests客户验收试验 CAXcentralaxis中央轴，中心轴 CBcircuitbreaker]断路器 CCcouchcontrol 床控制 CCPCAN calibrationprotocol CAN校准协议 CCTVclosed circuittelevision 闭路电视 CDcompactdisc CITP clients interface terminal panel (interface between Elekta product and client hardware)客户界面终端面板（Elekta产品与客户端硬件之间的接口） CMMcorrective maintenancemanual校正维护手册 CMUMClinical Mode User’s Manual 临床模式用户手册 CRPcommon referencepoint 公共参考点 CTComputerizedTomography计算机X射线断层
医用直线加速器比较表
医用直线加速器比较表 厂商Elekta VARIAN SIEMENS 说明 机型Precise Clinac EX Primus 基本结构Elekta加速器的高度集成化控制系统、性能绝佳的敞开式设 计保证可加速器的高开机率。其他厂家的产品都是封闭式设 计，常因机器设计不佳而停机，更换加速管时间长。 加速管行波驻波驻波最低的加速器使用消耗费用：驻波加速管对真空度的要求、能 量的转换、能谱的宽度等几个方面都优于驻波加速管。Elekta 保持和发展了行波管加速原理，通过独特的设计使一台加速器 可提供3档电子线。一机多用。其他厂家加速器最多产生两个 光子线。Elekta加速器具有低功耗、高效率、长寿命，自1953 年生产世界上第一台直线加速器以来，从未更换过加速管。 机架类型滚筒式中心轴承式中心轴承式Elekta滚筒机架磨损小，等中心变化小，十年精度1mm，终身 保证机架等中心精度在2mm（V和S都采用中心轴承式，十年 等中心偏差超过2mm），且为敞开式设计，散热性能好，连续 工作时间长，便于维修。 微波功率源仅用磁控管（ 5.5MW） 即可需速调管（5.5MW）加 微波驱动 需速调管（7MW）加 微波驱动 Elekta使用EEV公司的长寿命磁控管，停机时间短，运行费 用低，且无条件保修2年。 低运行费用的微波功率源：Elekta公司采用的微波功率源是 磁控管，集振荡器和放大器为一体，结构简单，不需额外的微 波振荡器（或微波驱动器）等组件，从而简化功率源的结构。 磁控管的体积小，能安装在机架上，直接把微波馈送到加速管， 不需特殊接头，且易更换，停机时间短（而速调管必须配上配 上微波振荡器才能实现磁控管的功能，磁控管的寿命比速调管 短一半，但由于振荡器的寿命与磁控管差不多，导致使用速调 管的费用为使用磁控管的4～5倍。
医用直线加速器
医用直线加速器 医用加速器是生物医学上的一种用来对肿瘤进行放射治疗的粒子加速器装置。带电粒子加速器是用人工方法借助不同形态的电场，将各种不同种类的带电粒子加速到更高能量的电磁装置，常称“粒子加速器”，简称为“加速器”。要使带电粒子获得能量，就必须有加速电场。依据加速粒子种类的不同，加速电场形态的不同，粒子加速过程所遵循的轨道不同被分为各种类型加速器。目前国际上，在放射治疗中使用最多的是电子直线加速器。 电子直线加速器 电子直线加速器是利用具有一定能量的高能电子与大功率微波的微波电场相互作用，能量电子直接引出，可作电子线治疗。电子打击重金属靶，产生韧致辐射，发射X射线，作X线治疗。 根据电子与微波电场的作用方式不同，电子直线加速器分为行波加速器和驻波加速器。 一个最简单的电子直线加速器至少要包括，一个加速场所（加速管），一个大功率微波源和波导系统，控制系统，射线均整和防护系统。当然市场上作为商品的设备要远比这些复杂，但这些基本部件都是必不可少的。医用加速器的分类 分类情况 医用加速器按照能量区分可以分为低能机、中能机和高能机。 按照X能量的档位加速器分为单光子、双光子和多光子。 低中高能机的区分主要在于给出的电子线的能量。 医用加速器用于放疗的适应症 1、当其用于常规放疗时其适应症为： 医用加速器适应症广泛，可用于头颈、胸腔、腹腔、盆腔、四肢等部位的原发或继发肿瘤，以及手术后残留的术后或手术前的术前治疗等。 西门子直线加速器 它所产生的高能X线具有照射深度强，射线集中等优点为，不仅能有效杀死癌细胞，而且能保护正常组织少受损伤，是治疗深部肿瘤的理想设备。它优于国产加速器，可以产生六档电子线，为肿瘤治疗提供了更好的方法。 高能X线具有皮肤损伤小，照射量高，保证正常组织效果好的特点，主要用于治疗深部肿瘤，高能电子束，能量可变，可根据不同的肿瘤深度进行调节选择，可用于恶性肿瘤和偏心性肿瘤的治疗，术中放疗也多用于高能电子束。 恶性肿瘤患者的治疗提倡的是综合治疗，放射治疗是不可缺少的手段，约有70%的患者需行放射治疗，医用直线加速器是现今国际上先进的放疗设备。 瓦里安直线加速器 该加速器融合了现代医学影像技术、立体定位技术、计算机、核医学、放射物理、自动化智能控制等多种现代高新科技，可实现对全身肿瘤的常规放射治疗、三维立体定向精确放疗、立体定向放射外科治疗(俗称X-刀治疗)、适形调强放射治疗(诺力刀治疗)等。该直线加速器能最大限度杀死肿瘤，保护人体正常组织提供更加准确、高效、安全的技术保障。 1具有双光子、多档能量的电子线，保证各种不同深度的肿瘤治疗剂量组要。肿瘤隐藏的再深，他也能像海底捞针一样抓住它2。具有多叶准直系统，能完成精确放疗计划。可从三维方向上随着肿瘤的不同形状变化，产生与肿瘤形状近似的照射体积，使治疗更精确。3。具有三维调强治疗计划系统，调强放射治疗是当今世界上
医科达Synergy医用直线加速器控制软件的工作原理与实际应用
中国医疗设备 2019年第34卷 08期 V OL.34 No.0872研究论著RESEARCH WORK 医科达Synergy 医用直线加速器控制软件的 工作原理与实际应用 杨晋，张灿，陈龙，江海 海军安庆医院 放射治疗技术部，安徽 安庆 246001 引言 医科达Synergy 医用直线加速器（以下称医科达加速器） 为数字化医用加速器，其具有快速治疗、自动摆位、调强 治疗、影像验证等功能，可开展常规放疗、适形放疗、静 态和动态调强放疗、图像引导调强放疗等，广泛应用于全 身各个部位的恶性肿瘤放射治疗[1-2]。 医科达加速器之所以称得上数字化，是因为其控制软 件包含七百多个Item ，用于实时监测和控制各子系统的运 行参数和状态；操作者可以通过控制软件里相关的Item 查 看机器参数或输入用户指令；当机器出现故障时，控制软 件会根据实时监测的信息自动诊断故障，并在显示器上显 示错误代码和故障信息。1 控制系统简介医科达加速器的控制系统主要由控制柜和三个控制区组成，控制柜与控制区之间通过两根1553串行线连接并通讯[3]。控制柜里包含两台工业计算机：显示处理器和控制处理器。图1所示为医科达加速器控制系统结构示意图。显示处理器里运行Integrity 应用程序，为操作者提供图 形用户界面（Graphical User Interface ，GUI ）,同时显示处 理器连接键盘、鼠标和显示器。因此，操作者不仅可以通过显示处理器的显示器查看机器参数和故障报错，还能通 过显示处理器的鼠标和键盘输入用户指令、修改校准参数。 [摘 要] 本文介绍医科达Synergy 医用直线加速器控制系统的基本结构和控制软件的工作原理，重点介绍控制软件的三类Item 及其Part 的工作原理及实际应用。首先介绍了医科达Synergy 医用直线加速器的控制系统的基本结构，接着介绍了控制软件里Item 和Part 的定义、分类和工作原理，最后通过分析高功率移相器的运动控制，说明了控制软件里Item 和Part 实际应用。操作者尤其是物理师和维修工程师应该熟练掌握相应的理论知识，以便在日常的工作中能通过控制软件的相关Item 快速准确地查看故障信息，查找机器运行参数，修改校准参数，分析解决问题等。 [关键词] 医科达加速器；控制系统；控制软件；医用直线加速器 Operating Principle and Practical Application of Elekta Synergy Medical Linac Control Software YANG Jin, ZHANG Can, CHEN Long, JIANG Hai Department of Radiotherapy Technology, Navy Anqing Hospital, Anqing Anhui 246001, China Abstract: This paper illustrated the basic structure of the control system and the operating principle of the control software of Elekta Synergy medical linac, and especially emphasized the operating principle and practical application of the Items and Parts housed in the control software. Firstly, this paper illustrated the basic structure of the control system of Elekta Synergy medical linac. Next, this article illustrated the definition, category and operating principle of items and parts in the control software. Finally, this article illustrated the practical application of Items and Parts in control software by analyzing the motion control of HP Phase Shifter. The operators, especially the service engineers and medical physicists, should master the relevant theory knowledge using the relevant items during their daily work, which is convenient for finding the error information, searching machine parameters, correcting the calibration parameters, and troubleshooting. Key words: Elekta linac; control system; control software; medical linac [中图分类号] R197.39 [文献标识码] A doi：10.3969/j.issn.1674-1633.2019.08.016 [文章编号] 1674-1633(2019)08-0072-04 收稿日期：2018-12-28 修回日期：2019-01-11 作者邮箱：aqpolo@https://www.wendangku.net/doc/4a11811004.html, 图1 医科达加速器控制系统结构示意图
医科达加速器离子泵监护装置的设计与实现
研究论著RESEARCH WORK 引言 随着放疗技术的发展，放疗作为肿瘤治疗的三大主要治疗手段之一，越来越受到广大肿瘤患者的认可，约有75%的患者需要采用放射治疗[1]。目前，国内外医院放疗用设备主要是瑞典的医科达和美国的瓦里安医用直线加速器，医科达加速器具有电子枪可拆卸的行波加速管，加速管内的真空度靠枪端和靶端的两个溅射式离子泵维持[2]。由于加速管可拆卸接口较多，密封度很难保证，两个离子泵必须24 h通电工作以维持加速管内真空度在10-6 mbar以下[3-4]。当发生断电几个小时以上，真空度下降[5]，来电后离子泵开始工作时负荷较大（或发生局部漏气时），泵体温度上升[6]。虽然工作电流大到一定值时，离子泵电源会因过流而自我保护，但此时离子泵的温度已达100℃以上，远远超出了其正常工作的温度[7-9]。如果不及时断电冷却，会严重影响其工作性能和使用寿命，甚至直接烧坏[10-12]。因加速器上没有对离子泵工作状态的指示和提示，工作人员对这种情况不能及时发现，直至加速管真空度下降到出现连锁保护。更危险的是夜间或周六、周日无人值班时发生以上情况。两个离子泵的价格50余万元，不但会导致严重的经济损失，而且影响病人的正常放疗。为解决这一问题，笔者设计了一种离子泵监护装置，可有效地避免以上情况的发生。 1 设计方法与工作原理 1.1 离子泵的结构 加速管真空系统是由枪端和靶端两个溅射式离子泵维持，其内部结构见图1。阳极为纵横排列的薄壁不锈钢筒，阴极为放置于阳极两端的两块钛板，阳极、阴极一起封装于不锈钢的外壳中，壳外加一U形永磁体，磁力线方向平行于阳极筒轴，垂直于阴极钛板。阴阳极之间加有7.3 kV 的直流高压，泵体内的残余气体分子在正交电磁场的作用下发生潘宁放电，产生的阳离子轰击阴极钛板，溅射出的钛原子在阳极筒内壁和阴极轰击较少的部位形成新鲜的钛 医科达加速器离子泵 监护装置的设计与实现 魏绪国1a，李修磊1a，王宏英1a，张明臣1b，王绪刚1a，王永明2 1. 聊城市人民医院 a. 放疗科；b. 设备科，山东聊城 252000； 2. 南京君茂医疗器械有限公司，江苏南京 210000 [摘 要] 目的 为避免医科达加速器离子泵高温损坏，及时发现工作异常，设计一种离子泵监护装置。方法选取我院小儿康根据枪靶端离子泵的工作特性和结构特点，设计一种有效的监护方法，并将各监护部件集成于监控箱内，安装在加速器机架的合适位置。结果经过应用检验，该装置实现了离子泵工作温度的实时显示、超温报警及断电保护功能，达到预设目标。结论离子泵监护装置安装简单可靠，能有效地保护离子泵，弥补了加速器设计的缺陷，避免了经济损失。 [关键词] 直线加速器；离子泵；真空度；离子泵监护装置 Design and Implementation of the Monitoring Device for the Elekta Accelerator Ion Pump WEI Xuguo1a, LI Xiulei1a, WANG Hongying1a, ZHANG Mingchen1b, WANG Xugang1a, WANG Yongming2 1. a. Department of Radiotherapy; b. Department of Equipment, Liaocheng City People’s Hospital, Liaocheng Shandong 252000, China; 2. Nanjing Junmao Medical Devices Co., Ltd., Nanjing Jiangsu 210000, China Abstract: Objective In order to avoid the high temperature damage of the Elekta accelerator ion pump and detect the abnormal work in time, a monitoring device of ion pump was designed. Methods According to the working characteristics and structural characteristics of the ion pump at the gun target, an effective monitoring method was designed. The monitoring components were integrated into the monitoring box and installed in the proper position of the accelerator frame. Results After application test, the device could realize real-time display of working temperature of ion pumps, over temperature alarm, and power failure protection function, suggesting the achievement of the preset target. Conclusion The ion pump monitoring device is simple and reliable, which can effectively protect the ion pump, make up for the defects of accelerator design, and avoid economic loss. Key words: linear accelerator; ion pump; vacuum degree; ion pump monitor [中图分类号]TH774 [文献标识码] A doi：10.3969/j.issn.1674-1633.2019.04.020 [文章编号] 1674-1633(2019)04-0076-04 收稿日期：2018-09-29 修回日期：2018-11-05 作者邮箱：sdlcwxg@https://www.wendangku.net/doc/4a11811004.html, 中国医疗设备 2019年第34卷 04期 V OL.34 No.04 76
医科达直线加速器参数(精)
Precise 全数字直线加速器 双模式的数字化加速器,提供宽范围的 X 线和电子线能量,充分满足放射治疗外照射的临床需要。 具有如下详述的特征和配置: 1.0 射线束能量 Precise 数字化加速器具有无可匹敌的多能量可定制性:2档 X 射线能量 (4~15MV 和 9档电子线能量(4~22MeV 2.0 Precise 全数字直线加速器主机系统包含如下特性: 独特设计的滚筒式机架直线加速器 -由强劲的刚性结构带来的高度可靠性和稳定性 -开放的机架结构,便于维修,需维护的重要部件均分布在易于接近的位置 -最低的等中心高度(124cm ,具有最优的临床可用性 -最大的等中心到治疗头的净空间距离 45cm 高效能的行波加速管 -行波加速管二十年无条件保用 -允许较低的电压梯度, 对行波加速管的真空要求低, 使电子枪等部件可快速拆卸并易于更换 大功率 FasTraQ 磁控管: -专门的紧凑型微波功率源, 5MW 功率输出,具有快速调谐的能力 -快速的束流切换特性 <0.1秒
-提供 24个月的保用期 独有的滑雪式偏转系统: -完全的消色散系统,并维持射束的对称性 -伺服控制的三极磁偏转系统 -精确的靶点聚焦,极佳的半影 可单独拆卸更换灯丝的电子枪 -电子枪伺服系统反应快速,确保束流能量的精度 -易于更换,维护费用低 六通道开放式结构的电离室 -最新型超薄壁陶瓷材料电离室 -自动校正 KTP (温度、湿度、气压 ,监测射线的剂量、对称性和平坦度-具有长期的高灵敏和高稳定性,适合精确的伺服控制射线束流 -重复精度:+/-0.5% -线性精度:+/-1% -2-10MU 时的线性精度对保证 IMRT 的放疗精度尤其重要 -旋转(运动束流投照时的稳定性:±1% -分辨率:0.1MU 运动系统 -用于操纵治疗头、机架及病人床的运动