September 20, 2006 -- 神經管母細胞瘤此一孩童最常見的惡性腦瘤之存活率，可在手術後藉精確治療而顯著獲得改善；這一個新方法包含了較低劑量的放射線和化學治療，比標準治療得到更好的效果，來自St. Jude's 孩童研究醫院的研究者在九月七日的Lancet Oncology期刊線上版發表此一報告。
主要作者St. Jude's醫院神經腫瘤科主任Amar Gajjar醫師在發表聲明時表示，我們現在不僅可以治癒約70%的高風險神經管母細胞瘤病童，還可以用一種較短且更方便的化療方式，治癒超過80%的這些有風險的孩童，我們把這些非常有前途的結果歸因於在手術後及早使用放射線治療 — 而不是等到化療之後— 且併用短期的密集的化療。
【目前為止最好的五年存活率】
目前美國的神經管母細胞瘤治療規範，是在完成放射線治療後給予12個月療程的化療；Gajjar醫師和同事設計一種新的處方，療程僅有四個月，使用僅有目前方式一半劑量的cisplatin (4次劑量取代原本的8次) 和四分之一的vincristine (8次劑量取代原本的32次) ，他們也降低一般平均危險性病患的放射線劑量，從36 Gy 降到23.4 Gy 。
儘管劑量減低，但是和之前的標準治療相比，新處方的存活率顯著改善。
Gajjar醫師和同事追蹤134位新診斷為神經管母細胞瘤的病患 (平均年紀7.6歲；範圍從3.1 –20.2歲) 達平均 5年(範圍從0.43 – 9.6 年)，病患被分成兩組 — 有一般風險疾病的86人，腫瘤完全切除且無證據顯示擴散到身體任一部位，以及有高風險疾病的48人，有惡性疾病或者術後殘留腫瘤大於1.5 cm2。
高風險組的整體 5年存活率和5年無事故存活率為70%，而以前所用的一年期化療處方則是得到55%，Gajjar醫師在訪談中向Medscape表示，我們的結果是迄今所有報告之中最好的。
一般風險組，整體5年存活率是85%，5年無事故存活率為83%，目前治療處方達到的存活率儘管有一些有較高的比率，但一般約在70%左右；Gajjar醫師建議，雖然存活率相似，但我們的處方採用較少的化療，因此毒性也降低許多，也比較不會打亂教育和家庭生活。
Gajjar醫師表示，有趣的是，在他和病童互動以及雙親的報告中，雖然不易量化，但是看起來短期治療處方的毒性較少；最壞的不良反應是使用vincristine出現的神經毒性，會影響腸等內臟神經，導致便秘，也影響週邊神經，導致行走困難，以及cisplatin引起的永久聽力損失。
Gajjar醫師表示，對於放射線治療後出現神經認知缺損小孩來說，這一點是極為嚴重的，這是小孩必須克服的許多難關之一。
【基因標記指向特定族群病患？】
未來的希望之一，是治療總量和因治療所致的毒性都可以更進一步降低，特別是那些反應更好或者預後更好的病患；此一研究的初步發現，如同其他研究，認為此類病患—神經管母細胞瘤的病患懷有CTNNB1 突變；研究者指出，他們可能表現一種分子的、和臨床不同的疾病類別，而有可較被接受的臨床結果；研究者認為未來的研究應該著重在減短療程。
Gajjar醫師強調，腫瘤組織之基因測試對未來的研究是非常重要的，他力主醫師和雙親在討論進行手術時確定此一要求。
Lancet Oncol.線上發表於September 7, 2006.
Better Survival in Medulloblastoma After Focused Treatment
By Zosia Chustecka
Medscape Medical News
September 20, 2006 — Survival rates after medulloblastoma, the most common malignant brain tumor in childhood, have been improved significantly by refinements in treatment following surgery. The new approach involves lower doses of both radiation and chemotherapy but has better results than standard treatment, researchers from St. Jude's Children's Research Hospital, Memphis, Tennessee, report in a paper published online September 7 in Lancet Oncology.
"Not only can we now cure about 70% of children with high-risk medulloblastoma, we can also cure more than 80% of those with standard-risk disease with a shorter, and therefore more convenient, chemotherapy approach," says lead author Amar Gajjar, MD, director of the neuro-oncology division at St. Jude's, in a press statement. "We attribute our very promising results to the early use of radiotherapy after surgery — rather than waiting until after chemotherapy — in combination with short-term, intense chemotherapy," he adds.
Five-Year Survival Rates Best So Far
In current US protocols for medulloblastoma, chemotherapy is given for about 12 months after completion of radiotherapy. Dr. Gajjar and colleagues devised a new regimen that lasted only 4 months, using half the amount of cisplatin (4 doses instead of 8) and only a quarter of the vincristine (8 doses instead of 32) used in current strategies. They also reduced the amount of radiation delivered, from 36 Gy to 23.4 Gy for average-risk patients.
Despite these reductions, survival rates with the new regimen were significantly improved when compared with those previously reported with standard treatment.
Dr. Gajjar and colleagues followed 134 patients with newly diagnosed medulloblastoma (average age 7.6 years; range, 3.1 – 20.2) for a median of 5 years (range, 0.43 – 9.6 years). The patients were divided into 2 groups — those with average-risk disease (86 patients), who had tumors completely resected and with no evidence of spread to any other part of the body, and those with high-risk disease (48 patients), who had metastatic disease or greater than 1.5 cm2 of residual tumor after surgery.
In the high-risk group, the overall 5-year survival and also the 5-year event-free survival were 70%, whereas the best that has been reported previously with the yearlong chemotherapy regimen is around 55%. "Our results are the best that have been reported so far," Dr. Gajjar told Medscape in an interview.
In the average-risk group, the 5-year overall survival was 85%, and the 5-year event-free survival was 83%. Current treatment regimens achieve survival rates of around 70%, although some groups have reported higher rates. "But even if the survival rates are similar, our regimen delivers much less chemotherapy with potentially much less toxicity, as well as less disruption to education and family life," Dr. Gajjar commented.
Anecdotally, from his interaction with the children and from parents' reports, there appears to be less toxicity with the shorter regimen, Dr. Gajjar comments, although this is difficult to quantify. Among the worst adverse events are neurotoxicity with vincristine, which affects the nerves in the gut, causing constipation, and also in the periphery, causing problems with walking, and permanent hearing loss with cisplatin. "This can be particularly devastating in a child that already has neurocognitive defects after the radiation," says Dr. Gajjar. "It's one more hurdle that the child must overcome."
Genetic Marker Pointing to Select Group of Patients?
One hope for the future is that the amount of treatment, and thus toxicity, could be reduced still further, particularly in certain patients who respond more favorably or who have a better prognosis. Preliminary findings from this study, as well as other research, suggest that there may be such a group of patients — those with medulloblastoma tumors harboring CTNNB1 mutations. They may represent a "molecularly and clinically distinct disease subset with a favorable clinical outcome," the researchers write, saying that further studies should explore treatment reduction in this group.
Dr. Gajjar emphasized that genetic testing of tumor tissue is very important for future research, and he urged physicians and parents to make sure to request this when surgery is being discussed.
Lancet Oncol. Published online September 7, 2006.
作者：
Zosia Chustecka 2007-6-20