左侧与右侧的结肠直肠癌有很大的差异


  【24drs.com】根据一个大型、由联邦政府资助之试验的分析,发生在左右两侧的结肠直肠癌之间有很大的差异,且原发肿瘤的位置会影响治疗选项。
  
  原发肿瘤在结肠左侧(在降结肠、乙状结肠和直肠)者的存活,显著比原发肿瘤位置在结肠右侧(在盲肠和升结肠)者更久;右侧肿瘤患者的整体存活期间(OS)中位数是19.4个月,左侧肿瘤患者是33.3个月。
  
  第一作者、旧金山加州大学医学教授Alan Venook医师表示,虽然之前的研究认为肿瘤位置可能会影响临床的结肠直肠癌结果,我们在这次试验中观察到的影响超乎我们的预期。
  
  他在声明中指出,即使我们寻求更深刻地理解生物学,这些研究结果将可能会改变结肠直肠癌的治疗与研究方法。
  
  Venook医师即将在美国临床肿瘤协会(American Society of Clinical Oncology[ASCO])2016年会发表这些新资料,他在会议前的记者会中讨论这些发现。
  
  这些新发现来自对「CALGB/SWOG 80405 (Alliance)」研究的进一步分析,研究对象是1,137名转移结肠直肠癌患者。这篇试验比较了第一线治疗之两种不同的化学治疗处方─oxaliplatin、5-fluorouracil与leucovorin (FOLFOX),以及irinotecan、5-fluorouracil与leucovorin (FOLFIRI)─以及两个标靶制剂,bevacizumab (商品名Avastin, Genentech, Inc药厂)与cetuximab (商品名Erbitux, ImClone Systems Incorporated药厂)。
  
  这篇试验的主要结果发表于ASCO 2014,指出这两个治疗组在无恶化存活(PFS)或整体存活(OS)之间没有差异,获得的结论指出,不论哪里种化学治疗处方或哪里种标靶制剂,都可用作第一线治疗。
  
  对这篇研究的追踪,发表于ASCO 2015,结论则是呈现出考虑成本上有哪里些变化。
  
  这次的新分析探讨的是原发病灶部位与患者之结果的关系。
  
  Venook医师报告指出,293名患者有右侧原发性肿瘤,732名患者是左侧原发性肿瘤。Venook医师解释,其它66名患者是横向肿瘤;这些患者被排除于分析,因为不论将他们纳入右侧肿瘤或左侧肿瘤,研究结果都没有差异。另外46名被认为不确定肿瘤位置的患者也被排除。
  
  纳入分析的所有患者的肿瘤都没有突变的KRAS基因,已知这个基因是对某些结肠直肠癌治疗,如cetuximab (事实上,cetuximab获核准只能用于这类患者)有反应的生物标记。
  
  初步分析显示,不论接受的治疗方法为何,相较于原发位置在右侧的患者,原发位置在左侧的患者有比较好的结果与比较长的存活。
  
  不过,进一步的探索性分析发现, 这些差异与治疗有关。
  
  在讨论时,Venook医师强调,接受cetuximab的患者中,左侧肿瘤者的OS中位数为36个月,右侧肿瘤者为16.7个月。
  
  他表示,这种差异幅度令我们吃惊。他指出,接受cetuximab的右侧肿瘤患者存活16个月左右,相较于其它各组是相当不同的,这显然是一个例外。
  
  探索性分析也发现, 接受bevacizumab的患者中,左侧肿瘤的整体存活期是31.4个月,右侧肿瘤者是24.2个月。
  
  Venook医师表示,从广义上讲,看来右侧结肠直肠癌患者未能从cetuximab治疗获益。他认为这个结果将会改变临床实务,这很可能代表一个转变。这些数据力主反对结肠直肠癌肿瘤位置在右侧的患者使用cetuximab和其它EGFR抗体,但现在,其它因素需要考虑。
  
  他指出,进一步的研究正在进行中。从参与这个试验的患者取得了44,000个肿瘤样本,继续进行更详细的分析,他希望这项研究将显示,患部侧是生物标记的替代品,目前患部侧可以帮我们对我们搜集的其它所有信息做出决定。
  
  这篇摘要的一名共同作者多了几分谨慎。芝加哥大学血液肿瘤科前主任、ASCO首席医疗官Richard Schilsky医师建议,这些是初步资料,需要加以确认。
  
  他评论指出,新资料认为左侧与右侧结肠直肠癌在生物上和解剖上都是不同的,他表示,可能有一些差异资料存在,但是,这是相当大型的一篇试验,有更确切的证据指出,这些都是我们应该关注的真正差异。
  
  Schilsky医师评论指出,结论的底线是,在未来,结肠癌研究的临床试验应根据患者的患部侧进行分组,以让我们更深入了解这个议题。
  
  他指出,我们还没准备好在实务上根据这个信息做出治疗决策,但它是相当有挑战性的,因为整体结果显示,标靶治疗的选择其实并不重要,这个新信息认为,根据患部侧时,它是重要的。
  
  ASCO理事长Julie M. Vose医师对这些新发现发表评论时表示,这是迄今有关结肠直肠癌患部的最大型研究,该研究极力认为这个意料之外的因素可以解答长久以来的问题-为何某些患者的效果比其它人更好。
  
  资料来源:http://www.24drs.com/
  
  Native link:Big Difference in Colorectal Cancer on Right vs Left Side

Big Difference in Colorectal Cancer on Right vs Left Side

By Zosia Chustecka
Medscape Medical News

"These findings will likely change the way we approach colorectal cancer treatment and research, even as we seek to more deeply understand the biology," he said in a statement.

Dr Venook will present the new data at the forthcoming American Society of Clinical Oncology (ASCO) 2016 Annual Meeting. He was discussing the findings at a premeeting presscast.

New Analysis of Data

The new findings derive from a further analysis of data from the CALGB/SWOG 80405 (Alliance) study, conducted in 1137 patients with metastatic colorectal cancer. The trial compared first-line treatment with two different chemotherapy regimens ─ oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX), and irinotecan, 5-fluorouracil, and leucovorin (FOLFIRI) ─ and two targeted agents, bevacizumab (Avastin, Genentech, Inc) and cetuximab (Erbitux, ImClone Systems Incorporated).

The main results from this trial, presented at ASCO 2014, showed no difference in either progression-free survival (PFS) or overall survival (OS) between any of the treatment arms, leading to the conclusion that either chemotherapy regimen and either targeted agent could be used as first-line therapy.

A follow-up to this, showing how a consideration of costs changes the conclusion, was reported at ASCO 2015.

This new analysis looks at patient outcomes with respect to where the original cancer was found.

Dr Venook reported that 293 patients had right-sided primary tumors, and 732 patients had left-sided primary tumors. An additional 66 patients had transverse tumors; these patients were excluded from the analysis, inasmuch as it made no difference to the results whether they were included among either the patients with right-sided tumors or those with left-sided tumors, Dr Venook explained. An additional 46 patients had tumors that were designated as uncertain; these patients were also excluded.

All the patients in this analysis had tumors without a mutated KRAS gene, which is a known biomarker of response to certain colorectal cancer therapies, including cetuximab (in fact, cetuximab is approved only for use in such patients).

The primary analysis showed that patients with colorectal cancer that originated on left side had better outcomes and longer survival than patients with cancer that originated on the right, regardless of the treatment they received.

However, a further exploratory analysis found differences that were related to treatment.

During the presscast, Dr Venook highlighted the finding that among patients who received cetuximab, those with left-sided tumors had a median OS of 36 months vs 16.7 months for patients with right-sided tumors.

The magnitude of this difference was "surprising to us," he said. He noted that this 16-month survival of patients with right-sided tumors who received cetuximab is "quite different" from what was seen in all the other subgroups. "It is clearly an outlier."

The exploratory analysis also showed that among patients who received bevacizumab, overall survival for those with left-sided tumors was 31.4 months vs 24.2 months for those with right-sided tumors.

"It appears that patients with right-sided colorectal cancer, broadly speaking, do not get benefit from cetuximab," Dr Venook said. He suggested that this finding will change clinical practice. "This could very well represent a shift," he said. Other factors need to be taken into consideration, but for now, these data argue strongly against using cetuximab and other EGFR antibodies in patients with colorectal cancer originating on the right side, he said.

He noted that further work is underway. Detailed, ongoing analysis is being conducted on 44,000 tumor samples taken from patients enrolled in this trial, and he hopes that this work will show that "sidedness" is a surrogate for biological markers. He said that for the time being, "The side can help us make decisions in the context of all the other information we gather."

A coauthor of the abstract was a little more cautious. "These are preliminary data and need confirmation," commented Richard Schilsky, MD, ASCO chief medical officer and former chief of the Section of Hematology-Oncology at the University of Chicago.

The new data suggest that left-sided and right-sided colorectal cancers are both biologically and anatomically different, he commented. "There have been some data trickling through that these differences may exists, but this was quite a large trial and is more definitive evidence to suggest that these are real differences that we should be paying attention to,” he told Medscape Medical News.

"The bottom-line conclusion is that in the future, clinical trials for colon cancer should stratify patients by 'sidedness,' so we can better understand this issue," Dr Schilsky commented.

"We're not ready yet to make treatment decisions on real-world practice based on this information, but it's pretty provocative...given that the overall results show that the choice of targeted therapy doesn't really matter. This new info suggests that it does matter, depending on sidedeness," he added.

Also commenting on the new findings, ASCO President Julie M. Vose, MD, said: "This is the largest study to date of tumor location in colorectal cancer, and it strongly suggests that this unexpected factor could answer some long-standing questions about why certain patients do better than others."

This study received funding and support from BMS, Genentech, and ImClone in collaboration with the National Cancer Institute. Dr Venook has received expenses from Halozyme, Genentech, Roche, Bristol-Myers Squibb, Merck, and Serono and institutional research funding from Bayer, Onyx, Genentech/Roche, Bristol-Myers Squibb, GlaxoSmithKline, Lilly. Several coauthors also report relationships with industry.

American Society of Clinical Oncology (ASCO) 2016 Annual Meeting: Abstract 3504,to be presented June 5, 2016.

    
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