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所有的癌症病患都要接受抗血栓预防吗？
(瑞典斯德哥尔摩) －静脉血栓(VTE)是癌症病患常见的问题，往往引起发病和致命，约有4%至20%的癌症病患发生，但相信这个比率可能低估了；虽有随机试验显示初步预防可以降低VTE，许多学会的专家指引也提出一些建议，执业肿瘤医师仍然有不同考量。
　　
　　因为癌症病患的VTE风险相当高，有些专家认为，VTE预防应扩及所有的癌症病患，包括门诊病患；相对的，其他人认为没有足够证据支持广泛用於这些病患，只可用在那些已知有风险因素者。两种论点都在第33届欧洲肿瘤医学会(ESMO)研讨会中的意见俱伸讨论会上发表。
　　
　　荷兰阿姆斯特丹Slotervaart医院肿瘤医师Hans-Martin Otten博士发表的论点，是预防应扩及所有的癌症病患，他指出，癌症病患的VTE依旧被低估且未予以治疗。
　　
　　Otten博士表示，癌症病患的VTE发生率相当高；在大多数的案例中，它未被认出；现在有有效的预防，花费低且出血风险低，我们为何不用？
　　
　　【用於手术与住院病患】
　　美国临床肿瘤医学会(ASCO)目前的指引是，接受大手术的癌症病患，住院的非手术癌症病患，在无出血或其他併发症时需考虑使用VTE预防；美国胸腔医学会(ACCP)的指引也建议久病的癌症病患才使用预防。
　　
　　Otten博士同意，他表示，肺栓塞[PE]经常引起住院病患死亡，是高风险病患促进抗血栓预防的主要原因之一；PE造成的住院死亡率约为12%；因此，不只致命的PE是重要的，有症状的VTE对於癌症病患也是重要的。
　　
　　英国Barts and the London医学牙医学院对外事务主任、手术科学中心主任Ajay Kakkar博士提出不同看法，他同意有许多状况的确需要使用抗血栓，特别是接受手术的癌症病患。
　　
　　Kakkar博士解释，VTE是手术癌症病患的常见问题，有明确的资料支持预防。
　　
　　不过，其他癌症病患类型的资料比较缺乏；Kakkar博士表示，非手术的住院癌症病患中，VTE的发生率相当广，因此不适合所有的病患都进行预防，我们需确认哪些人有风险，之后治疗他们。
　　
　　他指出，非手术癌症病患的VTE风险资料有限，虽然研究显示预防的确比安慰剂有明显利益，但是该试验中只有少数病患有癌症；Kakkar博士表示，对於癌症病患的结果是採取推论，现在我们还没有此一资讯。
　　
　　虽然指引建议非手术的住院病患必须考虑进行预防，Kakkar博士解释，医师需筛选哪些人有风险。
　　
　　【非卧床的门诊病患】
　　ASCO指引未建议对接受化疗的非卧床门诊病患进行常规预防，因为试验结果互相矛盾，可能会出血，需要检验监控与剂量调整，且这些人的VTE发生率相对较低。
　　
　　不过，Otten博士表示，这些病患也应进行预防；VTE不容易辨识，约有70%至80%的病患在院内死亡，连PE的诊断都没有，大部份的有症状PE发生在出院后、在门诊时，此时，医师无法经常看到病患的状况。
　　
　　Otten博士表示，有些报告显示，末期转移病患的有症状VTE发生率约为9%，但是无症状VTE的发生率超过50%。
　　
　　相反地，Kakkar博士认为，这类病患不需要常规预防，支持现有的指引；接受门诊化疗之病患的VTE风险未被充分研究，整体风险不高，我相信在筛选病患的判断和技巧上仍有问题，因此，不适合对非卧床的病患给予常规预防处方。
　　
　　【复杂的问题；各异的病患】
　　纽约罗彻斯特大学James P. Wilmot癌症中心医学助理教授Alok A. Khorana医师在访问中表示，这是一个复杂的议题，但显然的，相较於一般人，癌症病患的风险高出许多，不过，病患类型各异，风险并不相等。
　　
　　他表示，有些病患比其他病患风险高，主要的问题是没有针对癌症病患的研究；Khorana医师未参与ESMO的意见俱伸讨论；是由Medscape Oncology邀请他评论。
　　
　　他表示，癌症病患的VTE确切机转仍有待定义，肿瘤导致之VTE的实际发生率也不清楚；有许多共同风险因素，包括有无辅助治疗的化疗、无法行动、转移病灶、手术、肿瘤类型、有无某些共病症、有无中央静脉导管等。
　　
　　Khorana医师同意，虽然接受化疗之非卧床病患的VTE风险较高，但此风险各异；他向Medscape Oncology表示，有一些次组因为肿瘤类型和其他共病症而有较高风险，因此，聚焦在高风险次组是重要的。
　　
　　为了帮助辨识非卧床病患，Khorana医师等人使用开始的临床与实验变项，发展一种预测化疗相关VTE的简单模式；衍伸一种风险模式，并在1,365名癌症病患进行确认，结果显示，它可以辨识将近7%、有症状VTE短期风险的病患；此资料发表於5月15日的Blood期刊。
　　
　　【延长存活】
　　目前还无解的是，使用抗血栓治疗是否延长无VTE癌症病患的存活；Kakkar博士认为，很少有试验认为有存活利益。虽然有些结果令人鼓舞，但是结果各异，且一般显示只在某些次组分析时有临床利益。
　　
　　Kakkar博士表示，需要更简明的资料，现在不可能做出结论。
　　
　　第33届欧洲肿瘤医学会(ESMO) 研讨会。发表於2008年9月14日。

Should All Cancer Patients Receive Antithrombic Prophylaxis?

(Stockholm, Sweden) ?Venous thromboembolism (VTE) is a common complication in cancer patients, and a significant cause of morbidity and mortality. It occurs in approximately 4% to 20% of cancer patients, although it is believed that these rates are underestimates. Although randomized trials have demonstrated that primary prophylaxis can reduce VTE, and professional guidelines from several associations have issued a number of recommendations, there is still considerable variation among practicing oncologists in terms of compliance.

Because the risk for VTE is so high among cancer patients, some experts believe that VTE prophylaxis should be extended to all cancer patients, including those in the outpatient setting. Conversely, others feel that there is insufficient evidence to support universal use in this population and that prophylaxis should be administered only to those with known risk factors. Both sides of the issue were presented here in a point/counterpoint discussion at the 33rd European Society of Medical Oncology (ESMO) Congress.

Hans-Martin Otten, MD, PhD, who presented the argument for the use of prophylaxis in all cancer patients, pointed out that VTE remains underdiagnosed and undertreated in cancer patients. Dr. Otten is a medical oncologist at Slotervaart Hospital, in Amsterdam, the Netherlands.

\"There\'s a very high prevalence of VTE among cancer patients,\" said Dr. Otten. \"In most cases, it is not recognized. There is effective prophylactic treatment. It is low in cost and low in bleeding risk, so why don\'t we use it?\"

Use in Surgical and Hospitalized Patients

Current guidelines from the American Society of Clinical Oncologists (ASCO) recommend that cancer patients undergoing major surgery, along with hospitalized nonsurgical cancer patients, should be considered candidates for VTE prophylaxis in the absence of bleeding or other contraindications. Guidelines from the American College of Chest Physicians also recommend prophylaxis for bedridden patients with cancer.

Dr. Otten agrees: \"Pulmonary embolism [PE] is a frequent cause of death in hospitalized patients, and 1 of the primary reasons for promoting antithrombic prophylaxis in high-risk patients,\" he said. \"The in-hospital fatality rate from PE is about 12%. And not only are fatal PEs important, but symptomatic VTE is a burden for cancer patients.\"

Presenting the opposing viewpoint, Ajay Kakkar, MBBS, PhD, FRCS, agreed that there are a number of situations where the use of antithrombotics is warranted, especially among cancer patients undergoing surgery. Dr. Kakkar is professor and head of the Centre for Surgical Science and dean of external relations at Barts and the London School of Medicine and Dentistry, in the United Kingdom

\"VTE is a very common problem for surgical cancer patients, and there are really hard data to support prophylaxis,\" explained Dr. Kakkar.

However, the data for other types of cancer patients are less robust. Among nonsurgical hospitalized cancer patients, there is a wide range of VTE incidence. \"It is therefore inappropriate to offer all patients prophylaxis,\" said Dr. Kakkar. \"We should identify the subsets that may be at risk and treat them.\"

He pointed out that the data on VTE risk in nonsurgical cancer patients are limited. Although studies have shown a clear benefit of prophylaxis over placebo, only a small number of the patients included in these trials have had cancer. \"Results can be extrapolated for cancer patients,\" Dr. Kakkar said, \"but right now we just don\'t have the information.\"

Although guidelines do recommend that nonsurgical hospitalized patients should be considered candidates for prophylaxis, Dr. Kakkar explained that physicians need to be selective in choosing who is at risk.

Ambulatory Outpatients

ASCO guidelines do not recommend routine prophylaxis in ambulatory patients receiving chemotherapy because of conflicting trial results, potential bleeding, the need for laboratory monitoring and dose adjustment, and the relatively low incidence of VTE.

However, Dr. Otten argued that prophylaxis should be extended to this population as well. VTE is poorly recognized and, in about 70% to 80% of patients who die in the hospital, a diagnosis of PE was never considered, he explained. \"The majority of symptomatic PE occurs after discharge, in the outpatient setting, where doctors do not see patients very frequently.\"

Some reports show that the incidence of symptomatic VTE in patients with advanced metastatic disease is 9%, said Dr. Otten. \"But the rate of asymptomatic VTE is more than 50%.\"

Conversely, Dr. Kakkar felt that routine prophylaxis is not warranted in this population, and supported current guidelines. The risk for VTE among patients undergoing outpatient chemotherapy is not well studied, and the overall risk is not high, he said. \"I believe it is a question of our judgment and skills to select patients, rather than to prescribe it routinely to ambulatory patients.

Complicated Issue; Very Heterogenous Patients

\"This is a complicated issue, but it is clear that cancer patients as a whole have a much higher risk than the general population,\" commented Alok A. Khorana, MD, FACP, assistant professor of medicine at the James P. Wilmot Cancer Center at the University of Rochester, in New York. \"But this population is also very heterogenous, and the risk is not equally divided,\" he commented in an interview..

\"Some patients are at much higher risk than others, and the main problem is that no studies have been done specifically in cancer populations,\" he said. Dr. Khorana did not participate in the ESMO point/counterpoint discussion; he was approached by Medscape Oncology for comment.

The exact mechanisms of VTE in cancer patients are still being defined, and the actual prevalence of tumor-induced VTE is not known, he said. There are numerous confounding risk factors, including chemotherapy with or without adjuvant therapy, immobilization, metastatic disease, surgery, tumor type, presence of certain comorbidities, and the presence of central venous catheters.

Dr. Khorana agreed that although ambulatory patients on chemotherapy are at higher risk for VTE, the risk does vary. \"There are subgroups that are at higher risk because of the type of cancer and other comorbidities, and it is important to focus on the high-risk subgroups,\" he told Medscape Oncology.

To help identify that population among ambulatory patients, Dr. Khorana and colleagues developed a simple model for predicting chemotherapy-associated VTE, using baseline clinical and laboratory variables. A risk model was derived and validated in an independent cohort of 1365 cancer patients, and the results showed that it was able to identify patients with a nearly 7% short-term risk for symptomatic VTE. The data were published in the May 15 issue of Blood.

Prolonging Survival

An unanswered question is whether the use of antithrombotic therapy can prolong survival in cancer patients without VTE. There have been a few trials that did suggest a survival benefit, said Dr. Kakkar. Although some results have been encouraging, the results are variable and generally showed a clinical benefit only in subgroup analyses.

\"More concise data are needed, and it is not possible now to make recommendations,\" said Dr. Kakkar.

33rd European Society for Medical Oncology (ESMO) Congress. Presented September 14, 2008.

发布时间：2008年10月03日
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