旧金山——在美国临床肿瘤学会(ASCO)主办的新闻发布会上发布的一项回顾性研究显示，手术切除对伊马替尼治疗有应答的患者的残余胃肠间质瘤，可使至肿瘤进展时间显著延长至88个月，而单用伊马替尼者的至肿瘤进展时间仅为43个月。

　　在校正其他危险因素的影响之后，韩国首尔亚洲医疗中心的Seong Joon Park博士等人发现，手术可使疾病进展风险降低3/4，使死亡风险降低5/6。这一发现支持对此类患者切除残余肿瘤的通行做法。这场新闻发布会是在ASCO及其他3个癌症组织共同举办的胃肠肿瘤研讨会之前举行的。

　　研究者回顾分析了134例患者的数据。这些患者均在伊马替尼(格列卫)治疗后产生应答或保持病情稳定至少6个月，其中92例仅接受该药治疗，其余42例在伊马替尼中位治疗19个月后接受残余肿瘤切除术，术后再次接受伊马替尼治疗。所有患者接受中位时间59个月的随访。

　　“对于规模足够大、具有多学科小组经验、手术并发症和死亡风险足够低的医疗中心而言，这一治疗策略值得尝试。”

　　美国每年新诊断近5,000例胃肠间质瘤，尽管可累及消化道的任何部位，但最常见的是胃和小肠的间质瘤。一般以伊马替尼为一线治疗，80%~85%的患者对该治疗可产生应答。然而，对伊马替尼有应答的患者多数仍有残余肿瘤，后者可能参与耐药的发生，因此一些人推测切除残余肿瘤可改善生存。一般而言，根据肿瘤大小和其他的患者/肿瘤特征，1/3的患者适宜接受残余肿瘤切除手术。

　　本项研究中的两组患者的人口统计学特征相似，唯一的例外是手术组患者相对更年轻(51 vs. 58岁)、腹膜转移几率更低(41% vs. 61%)。由于手术有创且难度较大，因此医生更倾向于对体能状态较好的较年轻患者考虑和推荐手术治疗，而对多处腹膜转移的患者较少推荐。

　　多变量分析显示，与无进展生存期和总生存期较长相关的因素包括，手术和初始肿瘤尺寸＜150 mm。性别为女和有KIT外显子11突变，也与无进展生存期较长有关。研究者采用倾向性评分和逆概率加权校正来评估手术以外因素的效应。

　　胃肠肿瘤研讨会是由ASCO、美国胃肠病学会研究所(AGAI)、美国放射肿瘤学会(ASTRO)和肿瘤金宝搏版本 会(SSO)共同举办的。Park博士将在本次会议上报告研究结果，他报告称无相关利益冲突。

　　相关评论：分子靶向治疗加手术治疗

　　胃肠间质瘤是一种不常见的消化肿瘤，可在消化道中的多个部位发生。该病之所以引人注目，是因为伊马替尼分子靶向治疗的确对其有不俗的疗效。然而不幸的是，该药还是出现了耐药的情况。本项研究用令人兴奋的证据向我们表明，在伊马替尼内科治疗基础上采用积极外科手段，可能延长胃肠间质瘤患者的生存时间。

　　Neal J. Meropol博士是凯斯西储大学血液病与肿瘤学系主任。他是在新闻发布会上作为主持人发表上述评论的。他是Precision Therapeutics的顾问。

　　By: SHERRY BOSCHERT, Internal Medicine News Digital Network

　　SAN FRANCISCO – Surgically removing residual gastrointestinal stromal tumors in patients who respond to imatinib therapy significantly increased time to tumor progression to 88 months, compared with 43 months using imatinib alone, based on findings from a retrospective study of 134 patients.

　　After controlling for the effects of other risk factors, the surgery decreased threefold the likelihood of disease progression and decreased fivefold the risk of death, Dr. Seong Joon Park reported in a press briefing sponsored by the American Society of Clinical Oncology (ASCO). The press conference was held in advance of at a meeting on gastrointestinal cancers sponsored by ASCO and three other cancer organizations.

　　The findings support the widely adopted practice of removing residual tumors in these patients, despite the retrospective and observational design of the study, Dr. Park said. A prospective European study of similar design to this one terminated early due to poor patient enrollment. "It’s really hard to conduct a prospective study of this design," said Dr. Park of Asan Medical Center, Seoul, South Korea.

　　He and his associates reviewed the records of patients who showed at least 6 months of disease stabilization or response to imatinib (Gleevec) treatment, 92 of whom got the drug treatment alone and 42 of whom underwent surgery to remove residual tumors after a median of 19 months of imatinib therapy. The imatinib therapy was restarted after surgery. Median follow-up for the cohort as a whole was 59 months.

　　"This treatment strategy is worth trying as a clinical practice if the medical center is large enough to have an experienced multidisciplinary team and to have low morbidity and mortality associated with surgery," he said.

　　Each year, approximately 5,000 new cases of gastrointestinal stromal tumors are diagnosed in the United States, most often in the stomach and small intestine, though they can occur anywhere in or near the GI tract. Imatinib typically is first-line therapy, and 80%-85% of patients will respond to the treatment, he said. A majority of patients who respond to imatinib will have residual tumors, however, which are believed to contribute to the development of drug resistance, leading to the hypothesis that removing the residual tumors would improve survival.

　　In general, one-third of patients are candidates for surgical removal of residual lesions, depending on the tumor size and other tumor and patient characteristics, Dr. Park said.

　　The two patient groups in the study were similar except that the surgery group was significantly younger (51 vs. 58 years) and was less likely to have metastases in the peritoneum (41% in the surgery group vs. 61% in the control group).

　　As it is an aggressive and difficult treatment, surgery is more likely to be considered and recommended to younger patients who have a good performance status and, thus, less likely to be recommended in patients with multiple peritoneal metastases.

　　Factors associated with longer progression-free and overall survival included surgery and having an initial tumor size less than 150 mm, multivariate analyses showed. Female sex and having the KIT exon 11 mutation also were associated with longer progression-free survival. The researchers used propensity scores and inverse-probability-weighting adjustments to account for the effects of factors other than surgery.

　　The gastrointestinal cancers meeting, where Dr. Park will present the results, is cosponsored by ASCO, the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.

　　Dr. Park reported having no financial disclosures.

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　　Surgery adds to targeted molecular therapy

　　GI stromal tumors are an uncommon type of gastrointestinal tumor that can arise at many different places within the GI tract. This disease is notable because it’s really been a triumph of molecularly targeted therapy with imatinib (Gleevec), a drug that targets a particular molecular abnormality present in GI stromal tumors. Because of this, there is an extremely high response rate in patients with GI stromal tumors and drug therapy can control the disease for years.

　　Unfortunately, resistance ultimately develops to imatinib. This study provides provocative evidence that taking an aggressive approach surgically in addition to medical treatment with imatinib may result in longer survival of patients with GI stromal tumors.

　　Dr. Neal J. Meropol is chief of hematology and oncology at Case Western Reserve University, Cleveland. He gave these comments as moderator of the press briefing. He has been a consultant or advisor to Precision Therapeutics.