舊金山——在美國臨床腫瘤學會(ASCO)主辦的新聞發布會上發布的一項回顧性研究顯示，手術切除對伊馬替尼治療有應答的患者的殘餘胃腸間質瘤，可使至腫瘤進展時間顯著延長至88個月，而單用伊馬替尼者的至腫瘤進展時間僅為43個月。

　　在校正其他危險因素的影響之後，韓國首爾亞洲醫療中心的Seong Joon Park博士等人發現，手術可使疾病進展風險降低3/4，使死亡風險降低5/6。這一發現支持對此類患者切除殘餘腫瘤的通行做法。這場新聞發布會是在ASCO及其他3個癌症組織共同舉辦的胃腸腫瘤研討會之前舉行的。

　　研究者回顧分析了134例患者的數據。這些患者均在伊馬替尼(格列衛)治療後產生應答或保持病情穩定至少6個月，其中92例僅接受該藥治療，其餘42例在伊馬替尼中位治療19個月後接受殘餘腫瘤切除術，術後再次接受伊馬替尼治療。所有患者接受中位時間59個月的隨訪。

　　“對於規模足夠大、具有多學科小組經驗、手術並發症和死亡風險足夠低的醫療中心而言，這一治療策略值得嚐試。”

　　美國每年新診斷近5,000例胃腸間質瘤，盡管可累及消化道的任何部位，但最常見的是胃和小腸的間質瘤。一般以伊馬替尼為一線治療，80%~85%的患者對該治療可產生應答。然而，對伊馬替尼有應答的患者多數仍有殘餘腫瘤，後者可能參與耐藥的發生，因此一些人推測切除殘餘腫瘤可改善生存。一般而言，根據腫瘤大小和其他的患者/腫瘤特征，1/3的患者適宜接受殘餘腫瘤切除手術。

　　本項研究中的兩組患者的人口統計學特征相似，唯一的例外是手術組患者相對更年輕(51 vs. 58歲)、腹膜轉移幾率更低(41% vs. 61%)。由於手術有創且難度較大，因此醫生更傾向於對體能狀態較好的較年輕患者考慮和推薦手術治療，而對多處腹膜轉移的患者較少推薦。

　　多變量分析顯示，與無進展生存期和總生存期較長相關的因素包括，手術和初始腫瘤尺寸＜150 mm。性別為女和有KIT外顯子11突變，也與無進展生存期較長有關。研究者采用傾向性評分和逆概率加權校正來評估手術以外因素的效應。

　　胃腸腫瘤研討會是由ASCO、美國胃腸病學會研究所(AGAI)、美國放射腫瘤學會(ASTRO)和腫瘤外科學會(SSO)共同舉辦的。Park博士將在本次會議上報告研究結果，他報告稱無相關利益衝突。

　　相關評論：分子靶向治療加手術治療

　　胃腸間質瘤是一種不常見的消化腫瘤，可在消化道中的多個部位發生。該病之所以引人注目，是因為伊馬替尼分子靶向治療的確對其有不俗的療效。然而不幸的是，該藥還是出現了耐藥的情況。本項研究用令人興奮的證據向我們表明，在伊馬替尼內科治療基礎上采用積極外科手段，可能延長胃腸間質瘤患者的生存時間。

　　Neal J. Meropol博士是凱斯西儲大學血液病與腫瘤學係主任。他是在新聞發布會上作為主持人發表上述評論的。他是Precision Therapeutics的顧問。

　　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.