[淋巴癌] Early stage favorable Hodgkin's lymphoma相關臨床試驗整理

針對Early stage Hodgkin's lymphoma, 相關的臨床試驗非常多, 實際上NCCN 準則也是依照各個臨床試驗去決定劑量, Hodgkin's lymphoma在臨床放射治療上, 常常會遇到, 因此值得來整理!

Early stage Hodgkin lymphoma 就是所謂的 stage I, II, 其治療必須先依照病人是否有unfavorable risk factor 來分(之前的整理點此), 以下來整理Early stage favorable Hodgkin's lymphoma相關的臨床試驗

1. Early stage favorable Hodgkin's lymphoma:

(1) GHSG HD10 (NEJM 2010): 共收案1370個Early stage favorable Hodgkin's lymphoma病人, 分成四組, ABVD*4 + IFRT 30Gy,  ABVD*4 + IFRT 20Gy,  ABVD*2 + IFRT 30Gy,  ABVD*2 + IFRT 20Gy.   Primary end point 是 freedom from treatment failure; secondary end points 包括 efficacy and toxicity of treatment.

結果發現 ABVD*2 + IFRT 20Gy 的效果沒有比較差, 副作用相對較少 

=> 建立 ABVD*2 + IFRT 20Gy 是標準治療, 但是試驗時並沒有考慮用PET來評估化療反應, 因此後續又有其他臨床試驗

(2) Rapid trial (NEJM 2015): 收案病人皆為Early stage favorable Hodgkin's lymphoma病人, 想知道ABVD*3 後, 如果PET negative 的話, 是否要加上後續的放射治療(30Gy/15Fr), 實驗收案602個病人, 最後PET negative 且進入分組的有420位, 結果發現 3-year progression-free survival rate was 94.6% (95% confidence interval [CI], 91.5 to 97.7) in the radiotherapy group and 90.8% (95% CI, 86.9 to 94.8) in the group that received no further therapy, with an absolute risk difference of −3.8 percentage points (95% CI, −8.8 to 1.3). => 結論就是沒做RT 組的 3yr-OS 比較差, 因此RT不可省略

(3) EORTC H10 (JCO 2017): 收案病人皆為stage I, II 病人, 利用ePET去做評估, 所謂的ePET 即為 early PET 的意思, 意為接受ABVD*2 後去看治療反應, 收案裡有favorable跟unfavorable的病人, 主要是分成標準治療(standard arm) 以及 實驗組(experimental arm), 標準治療組病人接受ABVD*3 + INRT, 實驗組病人會利用PET 治療反應去決定後續治療, 如果PET negative, 後續繼續打ABVD*2, 如果PET positive, 後續給BEACOPPesc*2 + INRT

結果發現在ePET negative 的病人, ABVD*3 + INRT 的 ITT 5-year PFS rates 會比 ABVD*4 好(99.0% versus 87.1%, HR, 15.8 (95% CI, 3.8 to 66.1))

在ePET positive 的病人, 實驗是把 favorable 跟 unfavorable risk group 合在一起看治療結果, ABVD + INRT 的 ITT 5-year PFS rates 會比BEACOPPesc *2 + INRT 差(77.4% versus 90.6%, HR,  0.42 (95%CI, 0.23 to 0.74; P = .002)), 因此偏向把化療強度加強, 也就是BEACOPPesc *2 + INRT; 5-year overall survival (OS) rates were 89.3% versus 96.0% for ABVD + INRT and BEACOPPesc + INRT, respectively, with HR, 0.45 (95% CI, 0.19 to 1.07; P = .062)

(4) GHSG HD16 (JCO 2019): 共收案 1150 個 early stage favorable HL 的病人, 都在做過ABVD*2後進行治療反應評估, 標準治療組都接受20Gy IFRT, 實驗組如果PET negative (Deauville score < 3), 則省略後續放射治療, 結果發現在PET negative 組, 5-year PFS was 93.4% (95% CI, 90.4% to 96.5%) with CMT and 86.1% (95% CI, 81.4% to 90.9%) with ABVD (difference 7.3% [95% CI, 1.6% to 13.0%]; hazard ratio, 1.78 [95% CI, 1.02 to 3.12]). Five-year overall survival was 98.1% (95% CI, 96.5% to 99.8%) with CMT and 98.4% (95% CI, 96.5% to 100.0%) with ABVD.  => 結論就是ABVD*2 後, PET negative 去省略後續的20Gy IFRT, 5-yr PFS 明顯比較差

Reference:

1. ASTRO annual refresher's course

2. Engert A, Plütschow A, Eich HT, et al. Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma. N Engl J Med. 2010;363(7):640-652. doi:10.1056/NEJMoa1000067

3. André MPE, Girinsky T, Federico M, et al. Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial. J Clin Oncol. 2017;35(16):1786-1794. doi:10.1200/JCO.2016.68.6394