Ultrastaging of Early Colon Cancer

早期结肠癌的超分期

• 批准号: 8301475
• 负责人: ANTON J BILCHIK
• 金额: $ 26.04万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8301475
• 关键词: Adjuvant Chemotherapy; Adjuvant Therapy; Biological Assay; Biological Markers; Cancer Patient; Clinical Trials Cooperative Group; Collaborations; Colon; Colon Carcinoma; Data; Disease; Disease-Free Survival; Evaluation; Excision; Genetic Markers; Goals; Hematoxylin and Eosin Staining Method; Histologic; Immunohistochemistry; Incidence; Institutes; Lymphatic; Malignant Neoplasms; Maps; Micrometastasis; Military Personnel; Modeling; Molecular; Molecular Analysis; Molecular Genetics; Multivariate Analysis; Negative Staining; Neoplasm Metastasis; Nodal; Operative Surgical Procedures; Outcome; Pathologic; Pathological Staging; Pathologist; Pathology; Patients; Phase; Population Study; Primary Neoplasm; Prognostic Factor; Recurrence; Reporting; Resected; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; Sampling; Sampling Errors; Scientist; Sentinel Lymph Node; Sentinel Lymph Node Biopsy; Site; Specimen; Staging; Staining method; Stains; Study Subject; Techniques; Time; Tissues; Toxic effect; Transcript; Tumor Tissue; United States; base; candidate identification; chemotherapy; clinically relevant; improved; indexing; lymph nodes; malignant breast neoplasm; melanoma; molecular marker; mortality; outcome forecast; prognostic; prospective; public health relevance; randomized trial; tumor

DESCRIPTION (provided by applicant): The 20-30% rate of recurrence after surgical resection of stage II colon cancer (CC) suggests inadequate nodal sampling and/or inadequately sensitive and specific histologic assessment. Preliminary findings from our sentinel node (SN) study (CA 90484) demonstrate a 23% rate of nodal micrometastases (MM) missed by conventional sampling and histologic assessment. Our goal is to standardize the pathologic and surgical evaluation of stage II CC by focused analysis of a minimum number of nodes. We hypothesize that use of immunohistochemistry (IHC) and multimarker quantitative real-time PCR (qRT) assay to examine at least 12 LNs (a number recently endorsed by the National Quality Forum) will detect clinically relevant MM missed by standard hematoxylin and eosin (H&E) assessment of fewer than 12 nodes. In collaboration with the United States Military Cancer Institute (USMCI) Clinical Trials Group, which recently reported a Phase III randomized trial of nodal staging in CC, we will conduct a multicenter prospective trial of focused staging in 300 patients whose resected stage II CC specimens contain at least 12 nodes that stain negative with H&E. IHC will be performed and reviewed by USMCI pathologists, qRT assays and transcriptional analysis will be performed by UCLA scientists. Because patients will not receive adjuvant chemotherapy, we will be able to determine whether nodal MM identified by IHC and/or qRT have an impact on disease-free survival. As a corollary to this trial, we will also perform a comprehensive transcript analysis of the primary tumor specimens; the long-term goal is to create a prognostic index based on the primary tumor and LNs. This index should be helpful in identifying candidates for adjuvant therapy. Specific Aim I. To determine prospectively whether IHC and/or molecular (qRT) evidence of nodal MM in a specimen containing =12 H&E-negative LNs correlates with disease-free survival after resection of stage II CC. Specific Aim II. To evaluate the prognostic significance of molecular biomarkers detected in the primary tumor from patients with stage II CC. PUBLIC HEALTH RELEVANCE: Using quality surgery, standardized pathology and sophisticated molecular assays this trial will provide important information in determining which patients with early colon cancer are cured by surgery alone and which patients may benefit from chemotherapy.

描述(由申请人提供)：二期结肠癌(CC)手术切除后20-30%的复发率表明结节采样不足和/或组织学评估不够敏感和特异性。我们前哨淋巴结(SN)研究(CA 90484)的初步结果显示，常规采样和组织学评估遗漏了23%的结节微转移(MM)。我们的目标是通过集中分析最少数量的结节来标准化II期CC的病理和手术评估。我们推测，使用免疫组织化学(IHC)和多标记实时定量聚合酶链式反应(QRT)检测至少12个淋巴结(国家质量论坛最近认可的数字)将发现少于12个结节的标准苏木精-伊红(H&E)评估所遗漏的临床相关多发性骨髓瘤。与美国军事癌症研究所(USMCI)临床试验小组合作，最近报道了一项关于CC淋巴结分期的第三阶段随机试验，我们将在300名患者中进行一项重点分期的多中心前瞻性试验，这些患者的切除II期CC标本中至少有12个H&E染色阴性的淋巴结。由于患者不会接受辅助化疗，我们将能够确定IHC和/或QRT确定的结节性MM是否对无病生存有影响。作为这项试验的必然结果，我们还将对原发肿瘤标本进行全面的转录分析；长期目标是基于原发肿瘤和淋巴结创建一个预后指数。这一指标应该有助于确定辅助治疗的候选对象。具体目的1.前瞻性地确定标本中含有=12 H&E阴性淋巴结的结节MM的IHC和/或分子(QRT)证据是否与II期CC切除后的无病生存相关。具体目的II.评价分子生物标记物在II期CC患者原发肿瘤中检测的预后意义。公共卫生相关性：使用高质量的手术、标准化的病理学和复杂的分子分析，这项试验将提供重要的信息，以确定哪些早期结肠癌患者可以单独通过手术治愈，哪些患者可能从化疗中受益。

项目成果

Prognostic relevance of occult nodal micrometastases and circulating tumor cells in colorectal cancer in a prospective multicenter trial.

一项前瞻性多中心试验中结直肠癌隐匿性淋巴结微转移和循环肿瘤细胞的预后相关性。

• DOI: 10.1158/1078-0432.ccr-08-0290
• 发表时间: 2008-11-15
• 期刊: CLINICAL CANCER RESEARCH
• 影响因子: 11.5
• 作者: Koyanagi, Kazuo;Bilchik, Anton J.;Saha, Sukamal;Turner, Roderick R.;Wiese, David;McCarter, Martin;Shen, Perry;Deacon, Linda;Elashoff, David;Hoon, Dave S. B.
• 通讯作者: Hoon, Dave S. B.

Colorectal carcinoma nodal staging. Frequency and nature of cytokeratin-positive cells in sentinel and nonsentinel lymph nodes.

结直肠癌淋巴结分期。

• DOI: 10.5858/2003-127-673-ccns
• 发表时间: 2003
• 期刊: Archives of pathology & laboratory medicine
• 影响因子: 4.6
• 作者: Turner,RoderickR;Nora,DeanT;Trocha,StevenD;Bilchik,AntonJ
• 通讯作者: Bilchik,AntonJ

Thermal ablation of hepatic malignancy: useful but still not optimal.

肝脏恶性肿瘤的热消融：有用但仍不是最佳选择。

• DOI: 10.1016/j.ejso.2007.07.203
• 发表时间: 2008
• 期刊: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology
• 作者: Nicholl,MB;Bilchik,AJ
• 通讯作者: Bilchik,AJ

Targeted lymph node assessment in gastrointestinal neoplasms.

胃肠道肿瘤的靶向淋巴结评估。

• DOI: 10.1067/j.cpsurg.2013.09.001
• 发表时间: 2014
• 期刊: Current problems in surgery
• 影响因子: 4.4
• 作者: O'Connor,Victoria;Kitagawa,Yuko;Stojadinovic,Alexander;Bilchik,AntonJ
• 通讯作者: Bilchik,AntonJ

Value of primary tumor gene signatures in colon cancer when national quality standards are adhered to: preliminary results of an international prospective multicenter trial.

遵守国家质量标准时结肠癌原发肿瘤基因特征的价值：国际前瞻性多中心试验的初步结果。

• DOI: 10.1245/s10434-014-4013-y
• 发表时间: 2015
• 期刊: Annals of surgical oncology
• 影响因子: 3.7
• 作者: Bilchik,AntonJ;Wainberg,ZevA;Nissan,Aviram;Slamon,DennisJ;Protic,Mladjan;Avital,Itzhak;Chen,Hsiao-Wang;Chen,David;Sim,Myung;Elashoff,David;Stojadinovic,Alexander
• 通讯作者: Stojadinovic,Alexander