低血流、高代謝預測胰臟癌患者預後


  August 25, 2009 — 胰臟癌的治療仍然有限;這個疾病傾向於對許多治療具有抵抗性,例如全身性化學治療與放射線治療。然而,一項芬蘭研究結果顯示,灌流量下降可能解釋,至少部分解釋,何以胰臟癌放射線治療與化學治療的成功率有限。
  
  根據發表於臨床癌症研究期刊的研究,惡性與良性胰臟病灶,血流顯著地下降。相反的,代謝活性是增加的,但是僅有惡性腫瘤有這樣的現象。
  
  芬蘭Turku PET中心的一位研究員Gaber Komar醫師表示,代謝與血流比值高顯然可以預測較差的預後。
  
  Komar醫師向Medscape腫瘤學表示,血流與葡萄糖消耗不一致,可能代表某些腫瘤或是部分腫瘤能維持相對較高的代謝程度,儘管血流供給有限。這代表它們可能較能夠適應氧氣及養分不易取得的環境,因而更具侵入性、更難治療,致使這些病患的預後較差。
  
  根據這項研究的初期發現,研究者們表示,相較於僅功能性的測量,高代謝與血流比值可能預測較佳的存活率。他們表示,結合灌流與代謝造影應該包括在評估抗血管新生治療的研究中。
  
  David Mankoff醫師在一項聲明稿中指出,這些研究是該系列最新的一個,且已經證實腫瘤的血流/代謝不一致是對治療反應較差疾病的一個象徵,也是疾病預後較差的指標。Mankoff醫師是西雅圖華盛頓大學放射學、醫學與生物工程教授,他並未參與這項研究。
  
  Mankoff醫師表示,這項研究確認了胰臟腫瘤中存在著血流代謝不一致,與其他癌症相似,例如乳癌與肺癌,預測病患的預後較差。直到最近,我們才知道這個模式功能造影技術優點的結果。
  
  他附帶表示,這項研究發現應該引領研究者檢視腫瘤組織的氧合、缺氧在腫瘤臨床行為上以及對全身性治療反應所扮演的角色。
  
  【研究詳細內容】
  Komar醫師與其同事們想要使用氧15標記水與氟化去氧葡萄糖正子攝影(PET)/電腦斷層掃描非侵入性地定量胰臟腫瘤血流與代謝活性。他們表示,最可靠的非侵入性定量灌流量方法為使用氧15標記水的PET。
  
  這個族群包括26位病患:7位胰臟正常、8位有良性病灶、11位罹患惡性腫瘤。每位病患都接受胰臟血流與代謝測量,除此之外,計算標準化攝取值(SUV)與血流的比值。
  
  這些結果顯示,相較於正常胰臟組織受試者,良性與惡性腫瘤病患的病灶血流分別下降48%與60%。
  
  研究者也觀察到惡性腫瘤病灶的SUV與血流比值顯著比胰臟正常病患高(P<0.05)。除此之外,惡性腫瘤的SUVmax比良性病灶或正常組織高出三倍(P<0.05)。良性病灶病患的SUVmax與胰臟正常受試者沒有差異。
  
  Komar醫師表示,無疑的,需要一項收納更多病患的研究。一方面,這將確認我們的發現,另一方面,這將探索這些發現結合其他種類標靶治療、其他因子、腫瘤血管與可能考慮這些腫瘤內分佈參數的潛在預測價值。
  
  研究者們表示沒有相關資金上的往來。
  

Low Blood Flow, High Metabolism Predict Poor Outcome in Pancreatic Cancer

By Roxanne Nelson
Medscape Medical News

August 25, 2009 — Treatment for pancreatic cancer remains limited; the disease tends to be resistant to interventions such as systemic chemotherapy and radiation. However, findings from a Finnish study suggest that a decrease in perfusion might explain, at least in part, the limited success of both radiotherapy and chemotherapy in pancreatic cancer.

Blood flow was significantly decreased in both malignant and benign pancreatic lesions, compared with normal pancreatic tissue, according to the study published in Clinical Cancer Research. Conversely, metabolic activity was increased, but only in malignant tumors.

A high ratio of metabolism to blood flow appears to predict poor survival, note the authors, led by Gaber Komar, MD, a research fellow at the Turku PET Center in Finland.

"The blood-flow glucose-consumption mismatch might indicate that some tumors or parts of tumors are able to maintain relatively high metabolic levels, despite a limited blood supply," Dr. Komar told Medscape Oncology. This means that they are possibly better adapted to an environment with a low availability of oxygen and nutrients, and are therefore more aggressive and more difficult to treat, which results in poorer outcomes for these patients."

Based on the initial findings of this study, the researchers note that a "high ratio of metabolism to blood flow may predict survival better than either functional measurement alone." They suggest that combined perfusion and metabolism imaging should be included in clinical trials in which antiangiogenic treatment is being evaluated.

These results are the latest in a series of studies that have shown that a "mismatch" of blood flow/metabolism in tumors is a sign of resistant disease and a predictor of a poor outcome, David Mankoff, MD, PhD, pointed out in a press statement. Dr. Mankoff is professor of radiology, medicine, and bioengineering at the University of Washington in Seattle, and was not involved with the study.

"This study confirms that blood-flow metabolism mismatch exists in pancreatic tumors, similar to other cancers, such as breast and lung cancers, and predicts poor patient outcome," said Dr. Mankoff. "We've only recently recognized this pattern as a result of advantages in functional imaging methods."

He added that the findings presented in this study could lead researchers to examine the role that the oxygenation of tumor tissue and hypoxia play in mediating tumor clinical behavior and responsiveness to systemic therapy.

Study Details

Dr. Komar and colleagues attempted to noninvasively quantify the blood flow and metabolic activity of pancreatic tumors using oxygen-15-labeled water and fluorodeoxyglucose positron emission tomography (PET)/computed tomography scans. They note that the most reliable noninvasive method of quantifying perfusion is PET that uses oxygen-15-labeled water.

The cohort consisted of 26 patients: 7 with normal pancreases, 8 with benign lesions, and 11 with malignant tumors. Pancreatic blood flow and metabolism were measured in each patient and, in addition, the ratio of standardized uptake value (SUV) to blood flow was calculated.

The results showed that patients with benign and malignant tumors had decreased blood flow of the lesion by 48% and 60%, respectively, compared with those with normal pancreatic tissue.

The researchers also observed that the ratio of SUV to blood flow was significantly higher in malignant lesions than in benign lesions or in patients with a normal pancreas (P?< .05). In addition, the SUVmax was 3-fold higher in malignant tumors than in either benign lesions or in normal pancreases (P?< .05). The SUVmax did not differ between patients with benign lesions and those with a normal pancreas.

"There is no doubt a need for a study with a larger number of patients," said Dr. Komar. "On the one hand, it would confirm our findings, and on the other hand, it would explore the potential predictive value of these findings in combination with different types of therapy targeting, among other factors, tumor vasculature and possibly taking the intratumoral distribution of these parameters into account."

The researchers have disclosed no relevant financial relationships.

Clin Cancer Res. 2009;15(17):5511-5517.

    
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