Cloyd Jordan M, Wang Huamin, Egger Michael E, Tzeng Ching-Wei D, Prakash Laura R, Maitra Anirban, Varadhachary Gauri R, Shroff Rachna, Javle Milind, Fogelman David, Wolff Robert A, Overman Michael J, Koay Eugene J, Das Prajnan, Herman Joseph M, Kim Michael P, Vauthey Jean-Nicolas, Aloia Thomas A, Fleming Jason B, Lee Jeffrey E, Katz Matthew H G
Department of Surgical Oncology; University of Texas MD Anderson Cancer Center, Houston.
Department of Pathology; University of Texas MD Anderson Cancer Center, Houston.
JAMA Surg. 2017 Nov 1;152(11):1048-1056. doi: 10.1001/jamasurg.2017.2227.
We previously demonstrated that a major pathologic response to preoperative therapy, defined histopathologically by the presence of less than 5% viable cancer cells in the surgical specimen, is an important prognostic factor for patients with pancreatic ductal adenocarcinoma. However, to our knowledge, the patients most likely to experience a significant response to therapy are undefined.
To identify clinical factors associated with major pathologic response in a large cohort of patients who underwent preoperative therapy and pancreatectomy for pancreatic ductal adenocarcinoma.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective review of a prospectively maintained database at University of Texas MD Anderson Cancer Center. The study included 583 patients with histopathologically confirmed pancreatic ductal adenocarcinoma who received preoperative therapy prior to pancreatectomy between 1990 and 2015.
Preoperative therapy consisted of systemic chemotherapy alone (n = 38; 6.5%), chemoradiation alone (n = 261; 44.8%), or both (n = 284; 48.7%) prior to pancreatoduodenectomy (n = 514; 88.2%), distal pancreatectomy (n = 62; 10.6%), or total pancreatectomy (n = 7; 1.2%).
Clinical variables associated with a major pathologic response (pathologic complete response or <5% residual cancer cells) were evaluated using logistic regression.
Among all patients, the mean (SD) age was 63.7 (9.2) years, and 53.0% were men. A major pathologic response was seen in 77 patients (13.2%) including 23 (3.9%) who had a complete pathologic response. The median overall survival duration was significantly longer for patients who had a major response than for those who did not (73.4 months vs 32.2 months, P < .001). On multivariate logistic regression, only age younger than 50 years, baseline serum cancer antigen 19-9 level less than 200 U/mL, and gemcitabine as a radiosensitizer were associated with a major response. The number of these positive factors was associated with the likelihood of a major response in a stepwise fashion (0, 7.5%; 1, 12.7%; 2, 16.9%; 3, 35.7%; P = .009).
Although a major pathologic response occurs infrequently following preoperative therapy for pancreatic ductal adenocarcinoma, it is associated with a significantly improved prognosis. Of the patient- and treatment-related factors we analyzed, only young age, low baseline cancer antigen 19-9, and gemcitabine as a radiosensitizer were associated with a major pathologic response. Given its association with long-term survival, better predictors of response and more effective preoperative regimens should be aggressively sought.
我们之前证明，术前治疗的主要病理反应（通过手术标本中存活癌细胞少于5%进行组织病理学定义）是胰腺导管腺癌患者的一个重要预后因素。然而，据我们所知，最有可能对治疗产生显著反应的患者尚不明确。
在一大群接受术前治疗并因胰腺导管腺癌接受胰腺切除术的患者中，确定与主要病理反应相关的临床因素。
设计、设置和参与者：对德克萨斯大学MD安德森癌症中心前瞻性维护的数据库进行回顾性分析。该研究纳入了583例经组织病理学确诊的胰腺导管腺癌患者，这些患者在1990年至2015年间接受了胰腺切除术前的术前治疗。
术前治疗包括单纯全身化疗（n = 38；6.5%）、单纯放化疗（n = 261；44.8%）或两者联合（n = 284；48.7%），然后进行胰十二指肠切除术（n = 514；88.2%）、远端胰腺切除术（n = 62；10.6%）或全胰腺切除术（n = 7；1.2%）。
使用逻辑回归评估与主要病理反应（病理完全缓解或残留癌细胞<5%）相关的临床变量。
在所有患者中，平均（标准差）年龄为63.7（9.2）岁，53.0%为男性。77例患者（13.2%）出现主要病理反应，其中23例（3.9%）为病理完全缓解。主要反应患者的中位总生存时间显著长于无主要反应患者（73.4个月对32.2个月，P <.001）。在多因素逻辑回归分析中，只有年龄小于50岁、基线血清癌抗原19-9水平低于200 U/mL以及吉西他滨作为放疗增敏剂与主要反应相关。这些阳性因素的数量与主要反应的可能性呈逐步相关（0个因素，7.5%；1个因素，12.7%；2个因素，16.9%；3个因素，35.7%；P =.009）。
尽管胰腺导管腺癌术前治疗后主要病理反应发生率较低，但它与显著改善的预后相关。在我们分析的患者和治疗相关因素中，只有年轻、低基线癌抗原19-9以及吉西他滨作为放疗增敏剂与主要病理反应相关。鉴于其与长期生存的关联，应积极寻找更好的反应预测指标和更有效的术前治疗方案。
