左側與右側的結腸直腸癌有很大的差異


  【24drs.com】根據一個大型、由聯邦政府資助之試驗的分析,發生在左右兩側的結腸直腸癌之間有很大的差異,且原發腫瘤的位置會影響治療選項。
  
  原發腫瘤在結腸左側(在降結腸、乙狀結腸和直腸)者的存活,顯著比原發腫瘤位置在結腸右側(在盲腸和升結腸)者更久;右側腫瘤患者的整體存活期間(OS)中位數是19.4個月,左側腫瘤患者是33.3個月。
  
  第一作者、舊金山加州大學醫學教授Alan Venook醫師表示,雖然之前的研究認為腫瘤位置可能會影響臨床的結腸直腸癌結果,我們在這次試驗中觀察到的影響超乎我們的預期。
  
  他在聲明中指出,即使我們尋求更深刻地理解生物學,這些研究結果將可能會改變結腸直腸癌的治療與研究方法。
  
  Venook醫師即將在美國臨床腫瘤協會(American Society of Clinical Oncology[ASCO])2016年會發表這些新資料,他在會議前的記者會中討論這些發現。
  
  這些新發現來自對「CALGB/SWOG 80405 (Alliance)」研究的進一步分析,研究對象是1,137名轉移結腸直腸癌患者。這篇試驗比較了第一線治療之兩種不同的化學治療處方─oxaliplatin、5-fluorouracil與leucovorin (FOLFOX),以及irinotecan、5-fluorouracil與leucovorin (FOLFIRI)─以及兩個標靶製劑,bevacizumab (商品名Avastin, Genentech, Inc藥廠)與cetuximab (商品名Erbitux, ImClone Systems Incorporated藥廠)。
  
  這篇試驗的主要結果發表於ASCO 2014,指出這兩個治療組在無惡化存活(PFS)或整體存活(OS)之間沒有差異,獲得的結論指出,不論哪種化學治療處方或哪種標靶製劑,都可用作第一線治療。
  
  對這篇研究的追蹤,發表於ASCO 2015,結論則是呈現出考慮成本上有哪些變化。
  
  這次的新分析探討的是原發病灶部位與患者之結果的關係。
  
  Venook醫師報告指出,293名患者有右側原發性腫瘤,732名患者是左側原發性腫瘤。Venook醫師解釋,其他66名患者是橫向腫瘤;這些患者被排除於分析,因為不論將他們納入右側腫瘤或左側腫瘤,研究結果都沒有差異。另外46名被認為不確定腫瘤位置的患者也被排除。
  
  納入分析的所有患者的腫瘤都沒有突變的KRAS基因,已知這個基因是對某些結腸直腸癌治療,如cetuximab (事實上,cetuximab獲核准只能用於這類患者)有反應的生物標記。
  
  初步分析顯示,不論接受的治療方法為何,相較於原發位置在右側的患者,原發位置在左側的患者有比較好的結果與比較長的存活。
  
  不過,進一步的探索性分析發現, 這些差異與治療有關。
  
  在討論時,Venook醫師強調,接受cetuximab的患者中,左側腫瘤者的OS中位數為36個月,右側腫瘤者為16.7個月。
  
  他表示,這種差異幅度令我們吃驚。他指出,接受cetuximab的右側腫瘤患者存活16個月左右,相較於其他各組是相當不同的,這顯然是一個例外。
  
  探索性分析也發現, 接受bevacizumab的患者中,左側腫瘤的整體存活期是31.4個月,右側腫瘤者是24.2個月。
  
  Venook醫師表示,從廣義上講,看來右側結腸直腸癌患者未能從cetuximab治療獲益。他認為這個結果將會改變臨床實務,這很可能代表一個轉變。這些數據力主反對結腸直腸癌腫瘤位置在右側的患者使用cetuximab和其他EGFR抗體,但現在,其他因素需要考慮。
  
  他指出,進一步的研究正在進行中。從參與這個試驗的患者取得了44,000個腫瘤樣本,繼續進行更詳細的分析,他希望這項研究將顯示,患部側是生物標記的替代品,目前患部側可以幫我們對我們蒐集的其他所有資訊做出決定。
  
  這篇摘要的一名共同作者多了幾分謹慎。芝加哥大學血液腫瘤科前主任、ASCO首席醫療官Richard Schilsky醫師建議,這些是初步資料,需要加以確認。
  
  他評論指出,新資料認為左側與右側結腸直腸癌在生物上和解剖上都是不同的,他表示,可能有一些差異資料存在,但是,這是相當大型的一篇試驗,有更確切的證據指出,這些都是我們應該關注的真正差異。
  
  Schilsky醫師評論指出,結論的底線是,在未來,結腸癌研究的臨床試驗應根據患者的患部側進行分組,以讓我們更深入瞭解這個議題。
  
  他指出,我們還沒準備好在實務上根據這個資訊做出治療決策,但它是相當有挑戰性的,因為整體結果顯示,標靶治療的選擇其實並不重要,這個新資訊認為,根據患部側時,它是重要的。
  
  ASCO理事長Julie M. Vose醫師對這些新發現發表評論時表示,這是迄今有關結腸直腸癌患部的最大型研究,該研究極力認為這個意料之外的因素可以解答長久以來的問題-為何某些患者的效果比其他人更好。
  
  資料來源: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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