dodofo

作者：Roxanne Nelson  
出處：WebMD醫學新聞

　　November 26, 2009 — 對罹患胰臟神經內分泌腫瘤（PNTs）病患而言，放射線治療在達到局部控制與緩解上是有效的，它可以有效地緩解症狀。
　　
　　研究者們在11月15日的國際放射線腫瘤生物物理學期刊上報告，雖然一般認為PNTs這種腫瘤對放射線具有抵抗性，但結果顯示它對體外放射線治療（EBRT）具敏感性。
　　
　　作者們表示，由於PNTs的處理大都是根據過往的經驗，這項發現有點令人意外；他們也指出，已發表之病例報告資料，與這項研究結果相反，PNTs可能對於放射線與化學放射線治療是有反應的；PNTs經常代表一種無法切除的腫瘤，使得EBRT在處理這種疾病上是個吸引人的選擇。
　　
　　研究者安納堡密西根大學放射腫瘤部副教授Edgar Ben-Josef醫師表示，大家對使用放射線治療有錯誤的認知，但我們相信這是個好的緩和療法；我們進行這項研究來評估我們對此治療的經驗。
　　
　　【反應率與緩和成效佳】
　　他的團隊回顧了35位病患的病歷，這被認為是以EBRT治療PNTs的最大病患群。他們發現39%病患對放射線治療有反應，精算為有49%病患3年免於疾病惡化，且90%以上病患達到症狀緩解。
　　
　　Ben-Josef醫師向Medscape腫瘤學表示，我們建議臨床醫師們應該考慮對這些病患進行放射線治療，這是個有用的工具，但被低估了。
　　
　　【目前最大的病患群】
　　這些病患在1986至2006年間於49個位置接受放射線治療，研究者取得其中35位病患的病歷資料，14位病患接受原發腫瘤與腫瘤切除部位的放射線治療。在這群病患中，有8位病患的腫瘤無法以手術切除，6位接受外科手術切除仍遺留大部分病灶或邊緣仍殘留腫瘤（共3位），或是多處陽性淋巴結（共3位）。另外21位病患僅針對遠端轉移部位進行放射線治療，主要是肝臟與骨骼。
　　
　　接受原發性腫瘤部位治療組，幾乎所有病患（13位）都未接受過化學治療，其中大部分（共20位）接受遠端轉移部位放射線治療的病患，至少做了一個周期的化學治療。投予到原發性與遠端轉移部位的劑量中位數分別為58.4及24.6葛雷，這些病患中有32位接受症狀或疾病惡化治療。
　　
　　23位病患一共有26個部位接受治療，他們接受完整的電腦斷層掃瞄追蹤，其中10個部位是原發性腫瘤，16個是遠端轉移。在這組中，13%有完全反應，26%有部分反應，56%的疾病穩定，但有4%疾病惡化。
　　
　　【高劑量改善反應率】
　　Ben-Josef醫師表示，這確實有劑量相關反應。為了比較，所有放射線治療劑量都轉換為每次2葛雷的生物相等劑量（BED）。接受超過或低於BED2Gy中位數49.6的病患，比較其放射線診斷疾病惡化所需時間。作者們觀察到，這兩組之間有顯著差異（P<0.01）。
　　
　　此外，所有放射線診斷疾病惡化都發生在低於32 BED2Gy的病患身上。
　　
　　Josef醫師表示，我們需要使用較高的劑量來達到比較好的反應率；建議以精密的計畫技術，以及適當的劑量劃分療程進行治療。
　　
　　Josef醫師解釋，這仍有發生不良反應的可能，特別是進行比較積極的治療時。當然，我們並不希望傷害到我們的病患，但是我們的數據顯示這有劑量相關的治療反應。
　　
　　共有2個發生第四級毒性的病例，以及3件晚期毒性（其中2件屬於第三級，1件屬於第五級）；所有毒性反應都發生在接受開放傷口手術以及對原發部位腫瘤進行放射線治療的病患。這5位病患都接受超過50.4葛雷的放射線治療。
　　
　　整體存活時間中位數為2年，而在進行分析時，已有30位病患死亡。雖然原發部位與遠端轉移部位接受治療病患之間並無顯著差異，但接受原發部位治療的病患，有一年存活率較好的趨勢（86%相較於62%）。
　　
　　存活率並不是這項研究主要焦點，但我們可以說，這些病患的存活時間已經相當長。
　　
　　作者們表示已無相關資金上的往來。


Radiation Is Effective for Palliative Treatment of Pancreatic Neuroendocrine Tumors

By Roxanne Nelson
Medscape Medical News

November 26, 2009 — Radiation therapy is effective in achieving local control and palliation in patients with pancreatic neuroendocrine tumors (PNTs), and it produces high rates of symptomatic palliation.

In the November?15 issue of the International Journal of Radiation Oncology-Biology-Physics, researchers report that PNTs were sensitive to treatment with external-beam radiotherapy (EBRT), despite the fact that this type of tumor is often considered to be radioresistant.

We believe that it is a good palliative therapy.

The authors note that this perception is "somewhat surprising," considering the fact that the management of PNTs is limited to anecdotal experiences. They also point out that data from published case reports suggest just the opposite — that PNTs might be responsive to radiation therapy and chemoradiotherapy, and that PNTs often present as unresectable tumors, making EBRT an attractive option for managing the disease.

"There are misconceptions about the use of radiation, but we believe that it is a good palliative therapy," said study author Edgar Ben-Josef, MD, associate professor in the Department of Radiation Oncology at the University of Michigan in Ann Arbor. "We conducted this study to evaluate our experience with it."

High Rate of Response and Palliation

The team reviewed records for 35 patients, which is thought to be the largest case series of PNTs to be treated with EBRT. They found that 39% of patients experienced a response to radiation therapy, the actuarial 3-year local freedom from progression rate was 49%, and symptom palliation was achieved in 90% of the cohort.

"We recommend that physicians consider radiation therapy for these patients," Dr. Ben-Josef told Medscape Oncology. "It is an effective tool but is underutilized."

Largest Series to Date

These patients were treated with radiation therapy at 49 sites between 1986 and 2006. Of the 35 patients for whom records were available, 14 received radiation treatment to the primary tumor or tumor resection bed. Within this group, 8 patients had unresectable tumors and 6 underwent surgical resection with either gross residual disease left behind/positive margin (n?= 3) or multiple positive lymph nodes (n?= 3). The other 21 patients had only been treated at the sites of distant metastasis, predominantly the liver or bone.

Nearly all of the patients (n?= 13) in the group treated for a primary tumor were chemotherapy naive, and the majority (n?= 20) of those who received radiation treatment to metastatic sites had undergone at least 1 course of cytotoxic chemotherapy. The median dose delivered to the primary and metastatic sites was 58.4 and 24.6?Gy, respectively, and 32 patients in this cohort were treated for symptoms or for progressive disease.

Follow-up computed tomography scans were performed to evaluate the disease in 23 patients who received treatment at 26 sites — 10 to the primary tumor and 16 to metastatic sites. Of this group, 13% had a complete response, 26% had a partial response, 56% had stable disease, and 4% had progressive disease.

Higher Doses for Improved Response

There was a definite dose-related response, Dr. Ben-Josef said. For the purposes of comparison, all radiation doses were converted to a 2?Gy/fraction biologically equivalent dose (BED). The interval to radiographic disease progression was determined for patients receiving either greater than or less than the median BED2Gy of 49.6. The authors observed a significant difference between these 2 groups (P?< .01), and all cases of radiographic progression occurred in patients who had received a radiation dose of 32 BED2Gy or less.

"We need to use higher doses to achieve a better response rate," said Dr. Josef. "We recommend sophisticated planning techniques, as well as appropriate dose fractionation regimens."

There is a potential for adverse events, especially with more aggressive therapy. "We don't want to harm patients, of course, but our data showed a dose-response-related response to therapy," Dr. Josef explained.

There were 2 cases of acute grade?4 toxicities, and 3 late toxicities (2 that were grade?3 and 1 that was grade?5); all toxicities occurred in patients who had undergone both an open surgical procedure and radiation therapy to the primary site. All 5 patients received a radiation dose of more than 50.4?Gy.

The median overall survival was 2 years and, at the time this analysis was conducted, 30 of the patients had died. Although there were no significant differences between patients who were treated at a primary site and those treated at a metastatic site, and there was a trend for improved 1-year survival in those treated at the primary site (86% vs 62%).

"Survival was not the primary focus of our study, but we can say that the patients had a rather long survival," said Dr. Josef.

The authors have disclosed no relevant financial relationships.

Int J Radiat Oncol Biol Phys. 2009;75:1196-2000.