Comparison of Altered Fractionation and Conventional Radiotherapy for Primary Central Nervous System Lymphoma

傳統與多分次放射治療於原發性中樞神經系統淋巴瘤治療之比較

10.6316/TRO/200714(3)149

黃品逸(Pin-I Huang)；陳一瑋(Yi-Wei Chen)；陳盛鈺(Sheng-Yu Chen)；劉裕明(Yu-Ming Liu)；王令瑋(Ling-Wei Wang)；顏上惠(Sang-Hue Yen)；蕭正英(Cheng-Ying Shiau)

中樞神經系統 ； 淋巴腫瘤 ； 放射治療 ； 多分次放射治療 ； Central nervous system ； Lymphoma ； Radiation therapy ； Altered fractionion

放射治療與腫瘤學

14卷3期（2007 / 09 / 01）

149 - 163

英文

目的：評估原發性中樞神經系統淋巴瘤治療成效，並比較傳統與多分次放射治療的治療效益與治療相關毒性。 材料與方法：自1990年1月至2004年12月間，44位經由病理學或臨床上診斷為原發性中樞神經系統淋巴瘤的病人，於台北榮民總醫院癌病中心接受放射治療。計有29位男性與15位女性，平均年齡中位數為64歲（範圍，21-80）。所有病患依據其所接受的治療方式回溯性分成四組：1)傳統放射治療（每次1.8-2.5格雷，每天一次），15人；2)傳統放射治療合併化學治療，5人；3)多分次放射治療（每次1.2-1.5格雷，每天二次）17人；以及4)多分次放射治療合併化學治療，7人。所有的化學治療皆在放射治療之前給予，其中10位病患接受以methotrexate(MTX)為主的化學治療。病患的整體存活率(overall survival, OS)以及無惡化存活率(progression-free survival, PFS)是以Kaplan-Meier方法計算。各類別變項間是以log-rank test來比較。 結果：病患追蹤時間的中位數是24.3個月（範圍，2.7-83.1）。在可以評估反應的39位病患中，完全反應者有32位(82%)，部分反應者有5位(13%)。無惡化存活率中位數為18.9個月（95%信賴區間，10-27），預估的1年、2年與5年存活率分別為61%、40%與10%。整體存活率中位數為25.8個月（95%信賴區間，16-36），預估的1年、2年與5年存活率分別為75%、54%與15%。傳統放射治療與多分次放射治療在整體存活率（p值為0.28）與無惡化存活率（p值為0.14）上並沒有顯著差異。單變項分析顯示年齡、身體狀況（Karnofsky表現分數）與是否接受化學治療是重要的預後因子，但在多變項分析中只有年齡達到顯著性意義。年齡在64歲以下的病患，其整體存活率中位數為35.9個月，而64歲或64歲以上的患者，其整體存活率中位數只有18.9個月（p值為0.011）。Karnofsky表現分數高於或等於70分的患者的整體存活率中位數為32.2個月，明顯優於Karnofsky表現分數低於70分患者的13.1個月（p值為0.016）。 結論：多分次放射治療使用於原發性中樞神經系統淋巴瘤，對於疾病的控制、病患的存活率並沒有明顯的幫助。使用多分次放射治療可能有比較高的機會產生神經毒性。年齡與身體狀況是最重要的預後因子。對於原發性中樞神經系統淋巴瘤的病患，應根據其年齡與身體狀況選擇治療方式。

Purpose: To assess the treatment outcomes of primary central nervous lymphoma (PCNSL) treated with different radiotherapy (RT) fractionation strategies (conventional fractionation vs. altered fractionated radiotherapy) with or without systemic chemotherapy. Materials and Methods: Between January 1990 and December 2004, 44 patients with PCNSL (pathological or clinical) treated with curative radiotherapy at Taipei Veterans General Hospital were reviewed. There were 29 males and 15 females, with a median age of 64 (range, 21-80). Patients were retrospectively classified into 4 groups: 1) conventional fractionated radiotherapy alone (n=15); 2) combined conventional fractionated radiotherapy with chemotherapy (n=5); 3) altered fractionated radiotherapy (1.2-1.5 Gy per fraction, twice daily) alone (n=17); and 4) altered fractionated radiotherapy with chemotherapy (n=7). All chemotherapy, mostly (n=10) methotrexate (MTX) based regimens, were given before radiotherapy. Overall survival (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier method and subgroups were compared with log-rank test. Results: The median follow-up duration was 24.3 months (range, 2.7-83.1 months). Of the evaluable 39 patients, 32 patients (82%) obtained complete response and 5 patients (13%) had partial response. The median PFS was 18.9 months (95% confidence interval [CI], 10-27) with estimated 1-, 2- and 5-year PFS of 61%, 40% and 10%, respectively. The median OS was 25.8 months (95% CI, 16-36) with estimated 1-, 2- and 5-year survival rate of 75%, 54% and 15%, respectively. There was no significant difference in the OS and PFS between groups using conventional RT and altered fractionated RT regardless of chemotherapy (p=0.28 and 0.14, respectively). Age, Karnofsky performance status (KPS) and administration of chemotherapy were important prognostic factors in univariate analysis, but only age at diagnosis remained significant in multivariate model. Median survival was 35.9 months in patients younger than 64 and only 18.9 months in those aged 64 or older (p= 0.011). Patients with KPS ≥70 had a median survival of 32.2 months, which was longer than 13.1 months of patients with KPS ＜ 70 (p= 0.016). Conclusions: Altered fractionated radiotherapy is not beneficial in improving survivals of PCNSL. Age and performance status are most important prognostic predictors in PCNSL and should be taken into account in the selection of treatment modalities.