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作者：Zosia Chustecka  
出處：WebMD醫學新聞

　　December 2, 2009 — 對大腸直腸癌肝臟轉移且接受bevacizumab（Avastin）合併化學治療的病患，電腦斷層（CT）掃描顯示的轉移變化可以預測存活率。
　　
　　根據發表在12月2日美國醫學會期刊（JAMA）文獻的作者寫到，這些CT掃描上的變化被描述為「嶄新的」的發現。
　　
　　他們描述癌症轉移如何從異質性的團塊、有著不明顯的周圍，變成具同質性的低密度病灶且邊緣清楚。在部份病例上可能像是囊腫。研究者們附帶表示，這些改變，對於治療的反應，可能反映出接受治療的腫瘤被纖維結締組織取代，而非腫瘤壞死。
　　
　　在CT掃描上顯示對於術前治療有最佳型態學上改變的病患們，整體存活率增加。該團隊報告，CT變化與整體存活率之間的關係達統計上顯著差異。
　　
　　相反的，傳統以腫瘤大小評估的放射線檢查標準，固體腫瘤反應評估標準（RECIST），與存活率之間並沒有關係，這項標準被設計來評估接受細胞毒性治療後，腫瘤容積下降的反應。
　　
　　責任作者休士頓德州大學安德森癌症中心的Jean Nicholas Vauthey醫師表示，達最佳型態學改變的病患們，可以解除他們對治療好處的疑慮，即使腫瘤在這樣的標準下並未縮小。他向Medscape腫瘤學表示，對於治療有反應的病患們，接下來將有更多治療密集度較低、且能改善病患生活品質的選擇。
　　
　　【回溯性研究】
　　這些結果來自於一項分析50位病患的234處大腸直腸癌肝臟轉移，這些病患進行肝臟切除且接受術前bevacizumab及化學治療。所有病患在開始術前化學治療前與結束時都接受常規CT掃描。
　　
　　除此之外，研究者們分析另外82位罹患無法切除的大腸直腸肝臟轉移，且接受bevacizumab治療病患的CT掃描結果。
　　
　　這兩群病患都顯示CT掃描上有對術前治療最佳型態學上變化的，存活時間最長。
　　
　　那些接受肝臟切除的病患中，平均整體存活並未達到顯示最佳型態學上變化病患的水準；沒有或是反應不完全病患的整體存活時間中位數為25個月（P=0.03）。在非手術群病患中，有最佳型態學上變化病患的整體存活時間中位數為31個月，沒有或反應不完全病患的則是19個月（P=0.009）。
　　
　　除此之外，在CT掃描型態學上的改變與以完全、重大及輕微反應分類的病理反應有關；而RECIST標準與病理反應無關。
　　
　　研究作者們的結論是，我們的研究結果指出，型態學上的反應可能是有用的，病理反應的非侵入性替代標記與大腸直腸癌轉移接受包括bevacizumab療程的病患們存活時間較長。
　　
　　Vauthey醫師解釋，大約80%病患使用bevacizumab作為他們治療轉移起始治療的一部分。癌症轉移在CT掃描上的型態學變化在接受包括bevacizumab的化學治療療程後更加顯著，在我們的經驗中，接受其他生化製劑的病患，比較少見到這樣的反應。
　　
　　Vauthey醫師說表示接受Sanofi-Aventis、Genentech與Roche藥廠的研究經費與講師費。許多共同作者表示有相關資金上的往來，條列於文章中。


CT Changes in Colorectal Liver Metastases Predict Survival

By Zosia Chustecka
Medscape Medical News

December 2, 2009 — In patients with colorectal liver metastases who were treated with bevacizumab (Avastin) in combination with chemotherapy, computed tomography (CT) scans showed changes in the metastases that predicted survival.

The changes that showed up on the CT scans are described as "novel" by researchers writing in the December?2 issue of the Journal of the American Medical Association.

They describe how the metastases changed from "heterogeneous masses with ill-defined margins into homogeneously hypoattenuating lesions with sharp borders,?.?.?. which in some cases could mimic a cyst." These changes, on responding to treatment, "likely reflect the replacement of treated tumor by fibroconnective tissue rather than tumor necrosis," the researchers add.

Patients with an "optimal morphologic response" to preoperative therapy on the CT scans showed improved overall survival. The association between the CT changes and overall survival was statistically significant, the team reports.

In contrast, there was no correlation between survival and assessment by the traditional size-based radiological criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), which were designed to assess tumor volume reduction after cytotoxic chemotherapy.

"Patients with an optimal morphology response can be reassured that they are benefiting from treatment, even if the tumor isn't shrinking by standard size criteria," said corresponding author Jean Nicholas Vauthey, MD, from the Department of Surgical Oncology at the University of Texas M.D. Anderson Cancer Centre in Houston. "For patients with a cancer that is responding to therapy, there are more options for subsequently using less intense therapies that improve the patients' quality of life," he told Medscape Oncology.

Retrospective Study

The results come from a retrospective study that analyzed 234 colorectal liver metastases from 50 patients who underwent hepatic resection and who had received preoperative treatment with bevacizumab and chemotherapy. All patients underwent routine CT scanning at the start and end of the preoperative treatment.

In addition, the researchers analyzed CT scans for a separate validation cohort of 82 patients with unresectable colorectal liver metastases treated with bevacizumab-containing chemotherapy.

Patients in both cohorts who showed an optimal morphologic response to preoperative therapy on the CT scans had improved overall survival.

Among the patients who underwent hepatic resection, median overall survival was not reached in those who showed an optimal morphologic response; the median overall survival was 25 months for patients who had no or an incomplete morphological response (P?= .03). In the nonsurgical validation cohort, the median overall survival was 31 months in patients with an optimal morphological response and 19 months in those who had no or an incomplete morphological response (P?= .009).

In addition, the morphological response assessed on CT scans correlated with pathologic response, stratified as complete, major, or minor response. Again, the RECIST criteria did not correlate with pathologic response.

"Thus, our results indicate that morphological response may be a useful, noninvasive surrogate marker of pathological response and improved survival in patients with colorectal metastases receiving a bevacizumab-containing regimen," the authors conclude.

Dr. Vauthey explained that bevacizumab is used in about 80% of patients as part of their initial therapy for metastatic disease. The morphological changes in the metastases seen on the CT scan are "more pronounced" after treatment with chemotherapy that includes bevacizumab, he said, adding that, "in our experience, this response pattern is less common" in patients treated with other biological agents.

Dr. Vauthey reports receiving grants and honoraria from Sanofi-Aventis, Genentech, and Roche. Several coauthors have disclosed relevant financial relationships, as listed in the paper.

JAMA. 2009;302:2338-2344.