本帖最後由 p11111 於 2009-4-2 03:30 編輯
作者：Roxanne Nelson
出處：WebMD醫學新聞
March 13, 2009 — 根據3月7日Lancet期刊中發表的兩篇研究結果，短期的術前放射線對於可手術的直腸癌病患是一種有效的治療方式。
其中一篇研究結果顯示，術前放射線治療的局部控制與無病存活結果，比選擇性術後化學放射線治療較佳。第二篇研究中，研究者報告指出，不論在哪個平面要進行手術，術前短期放射線治療可以降低局部復發比率達50%以上。於直腸繫膜平面切除之病患，幾乎沒有局部復發。
此外，研究者指出，這些結果認為，藉由適當訓練的病理科醫師評估手術平面，可以確認局部復發之風險。
這兩篇研究的資料來自多中心的兩項試驗：Medical Research Council CR07和加拿大國家癌症研究中心的Clinical Trials Group C016。
明尼蘇達大學的Robert D. Madoff醫師在編輯評論中寫道，這些報告的主要訊息是，短期放射線治療降低直腸癌術後局部復發並非新見解。
Madoff醫師表示，許多之前的隨機試驗提供類似證據，這些資料確認了許多已廣為接受的觀察。
他指出，其中一個重要的觀察是，術前放射線治療可以緩和但無法消除不完美手術的副作用；最佳結果需是術前放射線治療加上適當的手術，但是，相反地，單只有適當的手術也無法完整解決局部復發。
CR07與C016這兩篇試驗對於直腸癌使用新輔助治療仍有無法解答的問題；他表示，輔助化學治療對於直腸癌的角色仍然未能有明確定義。Madoff醫師表示，術前放射線在直腸癌治療上已經證明其功能。下一個挑戰是，瞭解哪些病患需要此治療以強化其治癒機會。
【降低局部復發以及無病存活】
英國西約克夏聖詹姆斯腫瘤研究中心David Sebag-Montefiore所領導的第一篇研究中，研究者比較短期術前放射線治療與先手術再進行選擇性術後化學放射線治療。研究對象包括四個國家、80個中心的1,350名可手術的直腸腺瘤病患，初級結果是測量局部復發率。
隨機指派病患接受短期術前放射線治療(25 Gy分成5次；n= 674)，或者先手術再進行選擇性術後化學放射線治療(45 Gy分成25次，同時用5-fluorouracil)，限用於周圍邊緣切除的病患(n= 676)。
存活病患的平均追蹤期為四年，在分析期間，330名病患死亡；兩組的整體存活沒有顯著差異；術前組有157人死亡，選擇性術後組有173人死亡。發生局部復發的99名病患中，27人屬於術前放射線治療組，72人屬於選擇性術後化學放射線治療。
研究者觀察發現，接受術前放射線治療之病患的局部復發相對風險減少了61%，三年時的絕對差異為6.2%(術前放射線治療為4.4%、選擇性術後化學放射線治療為10.6%)。
術前放射線治療之病患的無病存活也有24%的相對改善，換算成三年時的絕對差異為6.0%(術前放射線治療為77.5%、選擇性術後化學放射線治療為71.5%)。
作者寫道，三年無病存活的顯著改善，似乎大部份可歸因於局部復發減少，不過目前並無整體存活差異的明顯證據。
第二篇研究中，研究者評估周圍邊緣切除範圍以及手術平面對於局部復發率的影響。
【手術平面的重要性】
主要作者、英國Leeds分子醫學研究中心、病理與腫瘤生物小組主任Phil Quirke博士表示，獲得最佳手術平面是重要的，可加強局部治癒的機會。短期放射線治療對於任何手術平面減少局部復發風險達半數。
他向Medscape Oncology表示，依照磁振造影分期選擇進行短期放射線治療的病患，他指出，第一期病患可能只需要手術，後期病患可能需要長期放射線治療與化療。
Quirke博士表示，介於中間者，則可考慮進行短期放射線治療。
研究對象包括CR07和C016試驗中，1,156名可手術的直腸癌病患，隨機指派接受術前放射線治療或者選擇性術後化學放射線治療。病理科醫師使用標準病理準則評估達成的手術平面、周圍邊緣切除範圍。
在這一組中，128名病患(11%)納入周圍邊緣切除範圍分析，手術平面則區分為良好(繫膜直腸)的有604名病患(52%)、適可(繫膜直腸間)的有398名病患(34%)、不良(固有肌肉層平面)的有154名病患(13%)。
研究者觀察發現，環狀切除邊緣陰性以及良好的手術平面與低復發率有關。三年時，環狀切除邊緣陰性者的局部復發率為6%，環狀切除邊緣陽性者為17%。
達成的手術平面也與局部復發率有強烈關聯。三年時，繫膜直腸組病患的局部復發率為4%、繫膜直腸間組為7%、固有肌肉層平面組為13%。接受術前短期放射線治療的病患，以及在繫膜直腸平面切除的病患，三年局部復發率只有1%。
作者指出，目前只有約50%的直腸癌手術在繫膜直腸平面進行，認為可藉由改善手術平面達到降低局部復發率的目標。
他們寫道，藉由手術與多元化團隊訓練可以繼續改善存活。
兩篇研究都接受英國的醫學研究委員會與加拿大國家癌症研究中心資助。許多作者受雇於醫學研究委員會；所有其他作者宣稱沒有相關財務關係。
Preoperative Radiation Therapy Reduces Rectal Cancer Recurrence
By Roxanne Nelson
Medscape Medical News
March 13, 2009 — A short course of preoperative radiotherapy is an effective treatment for patients with operable rectal cancer, according to the results of 2 studies published in the March 7 issue of the Lancet.
Results from 1 study showed that local control and disease-free survival are better with preoperative radiotherapy than with selective postoperative chemoradiotherapy. In the second study, researchers report that for any plane of surgery achieved, short-course radiotherapy prior to surgery reduces the rate of local recurrence by more than 50%. In patients who had a mesorectal plane resection, local recurrence was almost completely eliminated.
In addition, the researchers note, these results suggest that an assessment of plane of surgery achieved by an appropriately trained pathologist can be used to identify the risk for local recurrence.
The data from both studies come from the combined multicenter Medical Research Council CR07 and National Cancer Institute of Canada Clinical Trials Group C016 trial.
The main message from these papers, that short-course radiation therapy reduces the local recurrence rate after surgery for rectal cancer, is not new, writes Robert D. Madoff, MD, from the University of Minnesota, in Minneapolis, in an accompanying editorial.
A number of previous randomized trials have provided similar evidence, says Dr. Madoff, and these data confirm several well-accepted observations.
One important observation is "that preoperative radiation can mitigate but not eliminate the adverse effects of imperfect surgery," he notes. "The best outcomes occurred when preoperative radiation was followed by optimum surgery," but "conversely, optimum surgery alone was not the complete answer to local recurrence."
The CR07/C016 trial leaves unanswered questions about the use of neoadjuvant therapy in rectal cancer. The role of adjuvant chemotherapy for rectal cancer, he says, remains "surprisingly undefined."
"Preoperative radiation has proven its role in rectal cancer treatment," writes Dr. Madoff. "The next challenge is to understand which patient needs what therapy to maximize his or her chance for cure."
Reduction Seen in Local Recurrence and Disease-Free Survival
In the first study, led by David Sebag-Montefiore, MBBS, FRCP, FRCR, from St. James's Institute of Oncology, West Yorkshire, United Kingdom, the researchers compared short-course preoperative radiotherapy with initial surgery plus selective postoperative chemoradiotherapy. The cohort consisted of 1350 patients with operable adenocarcinoma of the rectum from 80 centers in 4 countries, and the primary outcome measure was local recurrence.
Patients were randomly assigned to short-course preoperative radiotherapy (25?Gy in 5 fractions; n?= 674) or to initial surgery with selective postoperative chemoradiotherapy (45?Gy in 25 fractions with concurrent 5-fluorouracil) that was restricted to patients with involvement of the circumferential resection margin (n?= 676).
The median follow-up for surviving patients was 4 years, and at the time of the analysis, 330 patients had died. Overall survival did not differ significantly between the 2 groups; there were 157 deaths in the preoperative group and 173 in the selective-postoperative group. Of the 99 patients who developed local recurrence, 27 received preoperative radiotherapy and 72 selective postoperative chemoradiotherapy.
The researchers observed a 61% reduction in the relative risk for local recurrence in patients receiving preoperative radiotherapy, and an absolute difference at 3 years of 6.2% (4.4% for preoperative radiotherapy vs 10.6% for selective postoperative chemoradiotherapy).
There was also a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy, which translates to an absolute difference at 3 years of 6.0% (77.5% for preoperative radiotherapy vs 71.5% for selective postoperative chemoradiotherapy).
"The significant improvement in 3-year disease-free survival seems to be predominantly attributable to the reduction in local recurrence," the authors write, although there is currently no clear evidence of a difference in overall survival.
In the second study, investigators assessed the effect of the involvement of the circumferential-resection margin and the plane of surgery achieved on rates of local recurrence.
Importance of Plane of Surgery
"Getting the best plane of surgery is important, as this optimizes the chance of local cure," said lead author Phil Quirke, PhD, head of the Section of Pathology and Tumour Biology at Leeds Institute of Molecular Medicine, in the United Kingdom. "Short-course radiotherapy reduces the risk of local recurrence by half for any given plane of surgery."
Short-course radiotherapy reduces the risk of local recurrence by half for any given plane of surgery.
"Patients should be selected for short-course radiotherapy depending on [magnetic resonance imaging] staging," he told Medscape Oncology, noting that stage?I patients may only need surgery and advanced patients may need long-course radiotherapy and chemotherapy.
"The middle group should be considered for short-course radiation treatment," Dr. Quirke said.
The cohort consisted of 1156 patients with operable rectal cancer from the CR07/C016 trial, who had been randomized to either preoperative radiotherapy or selective postoperative chemoradiotherapy. The plane of surgery achieved and the involvement of the circumferential-resection margin were assessed by pathologists, using a standard pathological protocol.
Within this group, 128 patients (11%) had involvement of the circumferential-resection margin, and the plane of surgery was classified as good (mesorectal) in 604 patients (52%), intermediate (intramesorectal) in 398 patients (34%), and poor (muscularis propria plane) in 154 (13%).
The researchers observed that a negative circumferential-resection margin and a superior plane of surgery were associated with low recurrence rates. At 3 years, the rate of local recurrence for patients with a negative circumferential margin was 6%, compared with 17% for patients with a positive circumferential margin.
The plane of surgery achieved was also strongly associated with the rate of local recurrence. A 3-year local recurrence rate of 4% was observed in the mesorectal group, 7% in the intramesorectal group, and 13% in the muscularis propria plane group. Patients who underwent preoperative short-course preoperative radiotherapy and who had a resection in the mesorectal plane had a 3-year local recurrence rate of only 1%.
Only about 50% of rectal cancer surgery is currently performed in the mesorectal plane, the authors note, which suggests "that a further decrease in local recurrence rates might be obtained by improving the plane of surgery achieved."
"Survival could be further improved by the use of surgical and multidisciplinary-team training," they write.
Both studies were funded by Medical Research Council (UK) and the National Cancer Institute of Canada. Several authors are employed by the Medical Research Council; all other authors have disclosed no relevant financial relationships.
Lancet. 2009; 373: 790-792, 811–820, 821–828. |
|
