低分次乳房放射线治疗显然是有效的

　　June 21, 2007（芝加哥訊）－目前為止，探索低分及乳房放射線療法的最大型研究已經發現，較少次、較大劑量與傳統療程在降低再發風險上是同樣有效的；這些研究結果發表於美國臨床腫瘤醫學會第43屆年會上。蘇格蘭Dundee大學John Dewar醫師向Medscape表示，我們看到更多有關投予較少、較大分次但整體劑量較低的策略，與投予50葛雷進行5星期的方式是一樣安全且有效的。
　　
　　在簡短發表這項發現的記者會中，擔任引言人的西雅圖華盛頓大學Julie Gralow醫師向記者表示，這些研究結果是有潛力的，且這樣的劑量療程是有意義的；在我們西雅圖的醫學中心中，有來自阿拉斯加接受治療的病患，且必須待在這個城市中；她表示，那些是我首先想要轉換至為期3週療程的病患。
　　
　　一位英國醫師在發表會後向研究者恭賀，這是項設計良好的研究，且結果很好；但是，儘管有這些新的證據，許多臨床醫師已經不願去改變放射線療法的療程。來自費城賓州大學的Lawrence Solin醫師向在座的聽眾表示，有許多原因使得這種加速乳房放射線治療並非那麼熱門，特別是在美國地區，他表示，高品質的長期研究都是以標準分次劑量進行，且有關於低分次治療已經發表的隨機分派臨床試驗並不多。
　　
　　Solin醫師在發表會後的討論時間表示，臨床醫師對於標準治療療程是最為熟悉的，對於較大每日劑量療程仍有許多晚期併發症的擔憂；對大部分病患而言，時間不是最重要的問題，且是否可以獲得放射線治療資源一般而言並不是個問題；他指出，放射線治療的併發症可以在治療之後數年或是甚至數十年後發生，因此建議特定的療程需要注意這些晚期併發症；但Solin醫師表示，如此一來，整體乳房加速放射線治療設計嚴謹的研究結果，將可以提供特定病患標準分次放射線療法之外的選擇。
　　
　　【不願意接受加速性放射線治療】
　　在與Medscape的訪談中，Dewar醫師同意醫學界有對於採用低分次放射線治療的疑慮；他表示，過去的研究數據已經證實，如果你以較大分次的方式，但未降低劑量，可能會有較高的發病率，這想當然爾的會使得病患變得謹慎；我們使用較低的劑量，結果顯示發病率是相當的。
　　
　　Dewar醫師附帶表示，有許多其他的研究，就像Ontario試驗，但這些研究的樣本數目小於我們的研究，且我認為臨床醫師合理地不想冒險，希望等待更大型的研究結果發布；這是證據上的另一個里程碑，我認為這將會使醫師對於可能是安全且有效的治療重燃信心。
　　
　　START（The Standardization of Breast Radiotherapy）研究是一項多中心、以美國、英國為主的第三期隨機分派臨床研究，對象為手術後接受放射線治療的病患，該項研究的目的在於檢驗低於2.0葛雷放射線治療，在早期乳癌病患的腫瘤控制、晚期正常組織反應、生活品質、與經濟效應。
　　
　　這項研究分為兩個部分，START試驗A包括2236位接受完全切除侵入性乳癌的婦女，這些婦女被隨機分派接受50葛雷於5週中分成25次進行的放射線治療、或是41.6葛雷於5週中分成13次的放射線治療，病患後續追蹤中位數5.1年。
　　
　　在試驗B中，2215位接受50葛雷於5週中分成25次、或40葛雷於3週中分成15次進行的病患，這些病患後續追蹤中位數為6年。
　　
　　【試驗A: 局部腫瘤再發】

放射線劑量 ( 葛雷 )	危險比值 (95% CI)	5 年時絕對差異， % (95% CI)
41.6 vs 50	1.05 (0.63 – 1.75)	+0.2 (-1.3 to 2.6)
39 vs 50	1.26 (0.77 – 2.08)	+ 0.9 (-0.8 to 3.7)

　　【試驗B: 局部腫瘤再發】

放射線劑量 ( 葛雷 )	危險比值 (95% CI)	5 年時絕對差異， % (95% CI)
40 vs 50	0.79 (0.48 – 1.29)	-0.6 (-1.7 to 0.9)

　　【嚴重不良反應】

結果	試驗 A ， n (%)	試驗 B, n (%)
嚴重急性反應	3 (0.1)	16 (0.7)
臂神經叢病變	1	—
症狀性肋骨骨折	29 (1.3)	34 (1.5)
症狀性肺纖維化	18 (0.8)	31 (1.4)
缺血性心臟疾病	45 (2.0)	46 (2.1)

　　在發表會中，Dewar醫師表示，這些研究結果支持乳癌與後期反應正常組織對於放射線治療分次是很敏感的，病患可以安全且有效地接受較低總劑量與較少分次的放射線治療。
　　
　　這樣的治療方式目前已經在英國許多醫學中心中進行，Dewar醫師表示，治療指引制定小組目前正在研議新標準，他也認同需要更多的研究來檢驗低分次放射線治療的限制，他預測這代表放射線療法進步的一個方向。

Hypofractionated Breast Radiotherapy Appears Effective

By Allison Gandey
Medscape Medical News

June 21, 2007 (Chicago) — The largest study to date to explore hypofractionation in breast radiotherapy has found that fewer, larger doses are as effective as conventional schedules in reducing the risk for recurrence. The results were presented here at the American Society of Clinical Oncology 43rd Annual Meeting. "We're seeing more evidence that giving fewer, larger fractions to a lower total dose is as safe and effective as giving 50-Gy fractions over 5 weeks," lead investigator John Dewar, MD, from the University of Dundee, in Scotland, told Medscape.

During a press briefing outlining the findings, moderator Julie Gralow, MD, from the University of Washington, in Seattle, told reporters that the results are promising and the dosing schedule makes sense. "At my center in Seattle, we have patients who come from Alaska for treatment and have to stay in the city. Those patients are the first that I would consider converting to a 3-week cycle," she said.

One United Kingdom–based physician attending the meeting congratulated the investigators after the presentation on "a superb trial and a good result." But despite new evidence, many clinicians have been reluctant to change radiotherapy schedules. Lawrence Solin, MD, from the University of Pennsylvania, in Philadelphia, told those attending the meeting that there are a number of reasons accelerated breast radiation has not become more popular — particularly in the United States. "High-quality long-term results are all with standard fractionation," he said, and there are few published randomized trials of hypofractionation.

"Clinicians are most familiar with standard schedules, and there has also been concern about the risk of late complications with large daily fractions," Dr. Solin explained during a discussion period following the presentation. "For most patients, time is not a major problem, and access to radiation is also not generally an issue." He pointed out that radiation complications could occur years or even decades after treatment, and so caution is advised in selecting treatment options. But, Dr. Solin noted, reported well-designed randomized trials such as this of whole-breast accelerated radiation provide an alternative to standard fractionation for selected patients.

Reluctance to Embrace Accelerated Radiation

During an interview with Medscape, Dr. Dewar agreed that there has been reluctance in the medical community to adopt hypofractionated radiotherapy. "Historical data have shown that if you give larger fractions without reducing the dose, you have higher morbidity, and that has understandably made people cautious," he said. "We used a lower dose and showed equivalent morbidity."

"There have been other studies, such as the Ontario study," Dr. Dewar added, "but that was smaller than ours, and I think clinicians understandably don't want to risk disadvantaging their patients and have been waiting for larger studies. This is another substantial block of evidence that I think will reassure physicians that this is now a potentially safe and effective way to go."

The Standardization of Breast Radiotherapy (START) trial is a multicenter United Kingdom–based phase 3 randomized controlled study of radiotherapy after surgery. The aim of the trial was to test the benefits of fraction sizes less than 2.0 Gy in terms of locoregional tumor control, late normal tissue responses, quality of life, and cost-effectiveness in patients with early breast cancer.

Divided into 2 studies, the START trial A looked at 2236 women who had completely excised invasive breast cancer. They were randomly assigned to receive either 50 Gy of radiation delivered in 25 fractions over 5 weeks or 41.6 Gy or 39 Gy delivered in 13 fractions on alternate days over 5 weeks. Patients were followed for a median of 5.1 years.

In trial B, 2215 women received either 50 Gy in 25 fractions over 5 weeks or 40 Gy delivered in 15 fractions over 3 weeks. Patients were followed for a median of 6 years.

Trial A: Locoregional Tumor Relapse

Gy	Hazard Ratios (95% CI)	Absolute Difference at 5 years, % (95% CI)
41.6 vs 50	1.05 (0.63 – 1.75)	+0.2 (-1.3 to 2.6)
39 vs 50	1.26 (0.77 – 2.08)	+ 0.9 (-0.8 to 3.7)

Trial B: Locoregional Tumor Relapse

Gy	Hazard Ratios (95% CI)	Absolute Difference at 5 years, % (95% CI)
40 vs 50	0.79 (0.48 – 1.29)	-0.6 (-1.7 to 0.9)

Severe Adverse Events

Outcome	Trial A, n (%)	Trial B, n (%)
Severe acute reactions	3 (0.1)	16 (0.7)
Brachial plexopathy	1	—
Symptomatic rib fracture	29 (1.3)	34 (1.5)
Symptomatic lung fibrosis	18 (0.8)	31 (1.4)
Ischemic heart disease	45 (2.0)	46 (2.1)

During his presentation, Dr. Dewar said these results support the hypothesis that breast cancer is as sensitive to fraction size as critical late-reacting normal tissues. And it is likely that patients can be safely and effectively treated to a lower total dose with fewer fractions.

The method is already being used in a number of UK centers, and Dr. Dewar reported that guideline development groups are working to establish new standards. While he acknowledged that additional trials are needed to test the limits of hypofractionation, he predicted that this represents the way of radiation therapy moving forward.

American Society of Clinical Oncology 43rd Annual Meeting: Late-breaking abstract 518. Presented June 4, 2007.