September 3, 2006 -- 一篇新研究显示，多次放射线治疗可改善存活率，且可以增加放射线剂量但无致命毒性；这篇报告登载于Lancet期刊，研究者发表一篇评估不依惯例的分次放射治疗对头颈
癌症好处的后设分析。
Lori Wirth、Aaron Allen和Mitchell Machtay等三位医师在该期刊的评论中指出，对存活率的改善虽小，但提供了每天一次的放射线治疗以外的替代原则；作者们是达那-法柏癌症研究治疗中心和Thomas Jefferson大学的医师，他们表示，对于整合头颈上皮癌治疗的其他改善研究和替代分次放射线治疗的挑战已往前迈进。
资深作者、法国Gustave-Roussy研究所的Jean-Pierre Pignon医师向Medscape表示，标准的头颈癌放射治疗是每天一次2 Gy、一周五天、疗程约七周，有15个研究针对此标准疗法和实验式疗法进行比较。
【快速的放射线治疗对潜在风险有用？】
Pignon医师表示，改成每天早上和下午各1.15 Gy、一周五天、疗程约七周，将可以有更好的局部控制和存活率，5年存活率从29% 增加到37%；因年纪增大而好处降低，在小于50岁者好处最大，50到69岁者则一般，70岁以上者则无好处。
头颈癌症放射治疗后设分析(Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck /MARCH) 合作团队的研究者，共研究超过 6500位病患，研究收纳之随机试验的平均追踪期是6年；Pignon医师指出各试验中的疗程各有不同 — 有些试验是比较同一疗程的不同剂量，有些是比较不同疗程的相同剂量，其他则是减少总剂量和总疗程。
Wirth、Allen和Machtay等三位医师认为，后设分析可以搜齐资料并整合各项结果之差异，是用来评估此类病患存活利益的适当工具；一如可预期的，[主要作者] Jean Bourhis 和同事的后设分析指出改善局部控制 (5年时分别是8.5% 和 1.9%)，转化成可测量的存活利益是5年3.4%，此结果可能比不上目前化学治疗可达到的8%。
在Medscape的访谈中，Pignon医师指出，虽然该后设分析中所收纳的试验研究设计和品质各有不同，他们仅对这些试验的结果加以比较，但各个试验中已对其各组病患进行比较，为了对此得到最佳结果， 我们针对此一问题采取公正的、可重复检测分析的分法搜集相关证据。
不过，Pignon医师补充，我们无法对毒性和顺从性有详尽研究，因为这些在各试验中并未以相同格式被纪录；他还指出多次放射线的花费也须再加以研究，让病患每一治疗日都还要多花半天，所造成的影响，可能是金钱所无法衡量的。
Fractionated Radiotherapy Improves Survival in Head and Neck Cancer
By Allison Gandey
Medscape Medical News
September 3, 2006 –- A new study shows that hyperfractionation improves survival and enables an increase in radiotherapy dose without life-threatening toxicity. Reporting in the Lancet, researchers present a meta-analysis evaluating the benefit of unconventional fractionated radiotherapy in head and neck cancer.
"The improvement in survival, while small, offers proof of principle that altered fractionation is better than once-daily radiotherapy," Lori Wirth, Aaron Allen, and Mitchell Machtay write in an accompanying comment in the journal. The authors are medical doctors from the Dana-Farber Cancer Institute, in Boston, Massachusetts, and Thomas Jefferson University, in Philadelphia, Pennsylvania. "The challenge moving forward will be how to integrate the advances of altered fractionated radiotherapy with other recent advances in the field of head and neck squamous-cell carcinoma treatment," they write.
"The standard radiotherapy for head and neck cancer is a treatment delivering 2 Gy in 1 fraction per day, 5 days a week, for about 7 weeks," senior author Jean-Pierre Pignon, MD, from the Institut Gustave-Roussy in Villejuif, France, told Medscape. "Fifteen trials have compared an experimental radiotherapy with this standard."
Is Accelerated Radiotherapy Worth the Potential Risk?
"Delivering radiotherapy in 2 fractions of about 1.15 Gy each (morning and afternoon), 5 days a week, for about 7 weeks, leads to better locoregional control and survival," Dr. Pignon said, adding that the 5-year survival rate increases from 29% to 37%. "The benefit decreases with age; it is larger in the population under age 50 years, average in the population aged 50 to 69 years, and probably nonexistent in the population aged 70 years or older."
The researchers, known as the Meta-Analysis of Radiotherapy in Carcinomas of Head and Neck (MARCH) Collaborative Group, looked at more than 6500 patients. The median follow-up for the randomized trials included in the study was 6 years. Dr. Pignon explained that the treatment schedules in the trials were variable — some trials compared different doses delivered in the same total duration, some compared the same dose delivered in different durations, and others reduced both the total dose and the total duration.
"Meta-analysis, with its ability to pool data and enhance power to detect small differences in outcomes, is a fitting tool to assess the question of survival benefit in this setting," Drs. Wirth, Allen, and Machtay comment. "As might be expected, [lead author] Jean Bourhis and colleagues’ meta-analysis indicates that improvements in local and regional control (8.5% and 1.9%, respectively, at 5 years) do seem to translate into a measurable survival benefit (3.4% at 5 years)." They add, "This result might not be as large as the survival benefit achieved with concurrent chemotherapy (about 8%)."
During an interview with Medscape, Dr. Pignon pointed out that although the trials included in the meta-analysis were diverse both in design and quality, their study compared only the results within the trials. "Patients from one arm of each trial are compared patients from the other arms of the same trial. To the best of our knowledge, we present all the available unbiased evidence on the question studied and the data presented allow reanalyses excluding some trials," he noted.
But, Dr. Pignon added, "We were unable to study toxicity and compliance in detail because these were not recorded in a compatible format in the different trials." He also pointed out that the cost of hyperfractionation needs to be studied. "Keeping patients for an extra half day every treatment day has a cost for the patient, which is not only monetary."
Lancet 2006; 368: 843-854.
作者：
Allison Gandey 2007-6-20