Patients with locally advanced adenocarcinoma of the esophagogastric junction have a better prognosis if their cancer shows an early metabolic response to preoperative chemotherapy, as detected by positron emission tomography, new data show.
In a prospective study known as MUNICON-2 that was conducted in Germany, 59% of patients had a PET-detected response after 2 weeks of chemotherapy, investigators said in a press briefing in advance of a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Even though the nonresponders were then given intensified treatment with chemoradiation, the responders were still more likely to be able to undergo curative resection and had a 4-year rate of progression-free survival that was twice as high as that of the nonresponders.
“Early metabolic response assessment, after only 2 weeks of preoperative chemotherapy, performed with fluorodeoxyglucose (FDG)-PET, is a feasible approach and allows for a response-guided treatment,” lead investigator Dr. Florian Lordick said in the press briefing.
“Unfortunately, we found that survival is still poorer in PET nonresponders, despite the addition of radiation,” he continued. “Therefore, we can conclude that early metabolic response assessment by FDG-PET allows us to identify patients with a very poor tumor biology.”
The investigators studied 56 patients with locally advanced, nonmetastatic adenocarcinoma of the esophagogastric junction of types I and II (cT3/4,Nx,M0). The patients underwent FDG-PET imaging before and after 2 weeks of platinum- and 5-fluorouracil-based chemotherapy.
They were defined as having a response if the tumor’s standardized uptake value decreased by at least 35%, according to Dr. Lordick, director of the department of hematology and oncology at Klinikum Braunschweig in Brunswick, Germany, and a senior lecturer at Hannover Medical School.
Responders received more of the same chemotherapy for a total duration of 3 months and then underwent surgery. Nonresponders were given salvage chemoradiation consisting of 32 Gy of external beam radiation therapy plus daily cisplatin, and then underwent surgery.
“The expectation was that by adding radiation therapy to those patients not responding to chemotherapy, we might improve their prognosis, we might improve local control, we might improve survival compared to historic controls,” he commented.
The 56 patients studied had a median age of 62 years; 91% were male, and 77% had an ECOG Performance Status score of 0. In terms of disease characteristics, 70% of patients had type I tumors, 93% had an ultrasound T3 stage, and 100% had clinically node-positive disease.
A PET-detected response to chemotherapy was found in 59% (33 patients). Responders were more likely than were nonresponders (23 patients) to be able to be able to undergo curative resection (82% vs 70%, respectively), although the difference was not statistically significant.
The rate of major histologic remission, defined as having less than 10% residual tumor, was also higher for responders (36% vs 26%).
After a median follow-up of 38 months, the 4-year Kaplan-Meier estimate of progression-free survival was about 60% for PET responders, compared with 30% for PET nonresponders.
Responders fared much better in terms of median event-free survival (not reached, vs 15.4 months) and median duration of overall survival (not reached, vs 18.3 months).
“The addition of radiation therapy has some local effect, as we saw in the resection specimens” from the nonresponders, Dr. Lordick commented. “But it seems that it was not strong enough to change the tumor biology of these patients.”
“The next step that we want to take now on a multicenter level within the EORTC (European Organisation for Research and Treatment of Cancer) is to ... study different alterations of treatment in PET nonresponders by adding an alternative chemotherapy regimen and new biologically targeted therapies,” concluded Dr. Lordick.
The study’s findings exemplify the use of predictors to individualize therapy, according to Dr. Jennifer C. Obel, moderator of the press briefing and a medical oncologist with the NorthShore University HealthSystem in Evanston, Illinois.
“This approach allows us to either stop therapies that have minimal benefit or continue those that are likely helping patients live longer,” she commented.
“Really, this study is quite intriguing because it demonstrates that patients with no response on PET scan after limited chemotherapy have a poor outcome,” said Dr. Obel. “Hopefully, in the future, we can use this technology to quickly move to other therapies and evaluate whether they are helping the patient or not.”
Dr. Lordick and Dr. Obel both reported that they did not have any relevant conflicts of interest.
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一项最新研究显示，如果正电子发射计算机体层显像(PET)显示局部进展期食管胃交界处腺癌对术前化疗呈现早期代谢性反应，则提示预后良好；而无反应的患者即使接受强化放化疗，预后仍然不良。
这项前瞻性研究(MUNICON-2)由德国Brunswick医院血液和肿瘤部主任、汉诺威医学院高级讲师Florian Lordick博士领衔完成，其结果在ASCO胃肠道肿瘤研讨会前的新闻发布会上公布。该研究纳入56例Ⅰ型和Ⅱ型局部进展期食管胃交界处腺癌(cT3/4,Nx,M0)患者。患者中位年龄为62岁，91%为男性，77%的患者ECOG功能状态评分为0。根据肿瘤特征，70%患者为Ⅰ型肿瘤，93%超声分期为T3期，100%临床检查淋巴结阳性。患者在接受以铂类或5-氟尿嘧啶为基础的化疗前和2周后分别进行氟脱氧葡萄糖(FDG)-PET成像检查，对化疗呈代谢性反应者继续完成3个月化疗后接受手术治疗，无反应者接受32 Gy外照射放疗加每日顺铂化疗的补救放化疗后接受手术治疗。
结果显示，PET检出59%患者(33例)对化疗呈早期代谢性反应(标准化摄入值下降35%以上)。有反应者能够接受根治性切除术的比例高于无反应者(82% vs. 70%)，但差异无统计学意义；有反应者的明显组织学缓解 (残存肿瘤小于10%)率也高于无反应者(36 vs. 26%)。在中位随访38个月后，有反应者Kaplan-Meier评估 4年无进展生存率(60% vs. 30%)、中位无事件生存时间(未到达 vs. 15.4 个月)和中位总生存时间(未到达 vs. 18.3 个月)均显著优于无反应者。
伊利诺斯州埃文斯顿北岸大学健康中心肿瘤专家Jennifer C. Obel博士认为，该研究表明PET可识别患者对化疗的应答情况，从而指导医生停止生存获益小的治疗，而继续开展可能有获益的治疗，堪称预测指标用于个体化治疗的典范。
Lordick博士和Obel博士均声称无利益冲突披露。
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