[肺癌] ASTRO 2018 palliative radiotherapy guideline

在肺癌的治療裡面, palliative RT 一直是一個重要的角色, ASTRO 針對這個議題, 在2018年的時候推出了準則, 雖然時間已經過去三年, 不過仍然是值得參考的資料, 以下就來細讀吧!

 KQ 1: CCRT 在肺癌palliative setting 的角色?

三期 NSCLC, 不適合curative therapy, 但是符合以下條件

(1) candidates for chemotherapy
(2) have an Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2
(3) have a life expectancy of at least 3 months

=> 可以給palliaitve CCRT

evidence 的話, ASTRO guideline 是依照三篇RCT, 都是palliaitve setting 下去比較CCRT versus RT

Stage IV NSCLC:

沒有證據CCRT可以使用在palliative setting

References:

1. Moeller, B., Balagamwala, E. H., Chen, A., Creach, K. M., Giaccone, G., Koshy, M., Zaky, S., & Rodrigues, G. (2018). Palliative thoracic radiation therapy for non-small cell lung cancer: 2018 Update of an American Society for Radiation Oncology (ASTRO) Evidence-Based Guideline. Practical radiation oncology, 8(4), 245–250. https://doi.org/10.1016/j.prro.2018.02.009

[軟組織肉瘤] retroperitoneal sarcoma 術前是否需要放射治療(EORTC-62092: STRASS)

在 retroperitoneal sarcoma 裡面, 手術一直是標準治療, 在手術前是否需要加上術前放射治療, 一直是個有爭議的主題, 在2020年底, Lancet oncology 發表了關於這個主題的重要研究, 雖然一年過去了, 但是這個臨床試驗還是很重要, 因此這邊來做個整理!

這個臨床試驗是phase III RCT, 總共在31個地方進行收案, 收案條件為18歲以上, 收案條件為組織學上確認的priamry soft tissue sarcoma of retroperitoneal or infraperitoneal spaces of the pelvis.

總共分成兩組, 分別為en bloc surgery versus pre-operative radiotherapy + en bloc surgery

Primary endpoint 定為 abdominal recurrence free survival

Secondary endpoint 定為 tumor response to preoperative radiotherapy, metastasis-free survival, abdominal recurrence free interval, overall survival, safety and quality of life.

結果總共收案266人, 分為兩組, 各133人, 結果發現abdominal recurrence free survival在兩組統計上並沒有差異[HR=1.01(95% CI 0.71-1.44), log-rank p=0.95]

副作用方面, 最常見的 grade 3–4 adverse events 是 lymphopenia (98 [77%] of 127 patients in the radiotherapy plus surgery group vs one [1%] of 128 patients in the surgery alone group), anaemia (15 [12%] vs ten [8%]), and hypoalbuminaemia (15 [12%] vs five [4%]). 

Serious adverse events were reported in 30 (24%) of 127 patients in the radiotherapy plus surgery group, and in 13 (10%) of 128 patients in the surgery alone group. One (1%) of 127 patients in the radiotherapy plus surgery group died due to treatment-related serious adverse events (gastropleural fistula), and no patients in the surgery alone group died due to treatment-related serious adverse events.

=> 從上面的結果可以發現局部控制差不多, 但是副作用在RT 組明顯比較多,  因此這篇RCT認為不應該在手術前加上放射治療

Reference:

1. Bonvalot, S., Gronchi, A., Le Péchoux, C., Swallow, C. J., Strauss, D., Meeus, P., van Coevorden, F., Stoldt, S., Stoeckle, E., Rutkowski, P., Rastrelli, M., Raut, C. P., Hompes, D., De Paoli, A., Sangalli, C., Honoré, C., Chung, P., Miah, A., Blay, J. Y., Fiore, M., … Haas, R. L. (2020). Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial. The Lancet. Oncology, 21(10), 1366–1377. https://doi.org/10.1016/S1470-2045(20)30446-0

[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

[肺癌] 小細胞肺癌 PCI 做hippocampus sparing 是否有幫助

目前針對全腦照射是否需要做海馬迴閃避已經有好幾篇相關的研究, 例如 RTOG 0933(先前整理點此), NRG-CC001(先前整理點此). 但是上面的研究都是針對腦轉移, 而不是針對小細胞肺癌的預防性顱部照射(PCI)去做的研究! 因此針對小細胞肺癌的預防性顱部照射是否需要做海馬迴閃避, 有以下兩篇研究, 以下就來細讀!

1. PREMER trial: 共收案150人, SCLC (71.3%是limited stage), 隨機分成兩組, 一組接受PCI with hippocampus avoidance, 另一組接受PCI without hippocampus avoidance, PCI 的劑量是25Gy/10Fr, primary endpoint 是在做完放射治療第三個月的時候使用Free and Cued Selective Reminding Test (FCSRT)量表去看delayed free recall (DFR), 下降三分以上就代表有意義; 其他的endpoint包括FCSRT scores, quality of life, evaluation of the incidence and location of brain metastases, and overall survival (OS). 紀錄baseline以及在放射治療結束後的 3, 6, 12, and 24 個月的資料.

median follow-up time for living patients was 40.4 months, 結果發現PCI with hippocampus avoidance 顯著改善認知功能, 在其他指標, 包括brain failure, OS, and QoL 沒有差異. 

2. NCT01780675: 共收案168人, SCLC (70%是limited stage), 隨機分成兩組, 一組接受PCI with hippocampus avoidance, 另一組接受PCI without hippocampus avoidance, PCI 的劑量是25Gy/10Fr, primary endpoint 是在做完放射治療第四個月的時候使用Hopkins Verbal Learning Test-Revised量表去看total recall, 下降五分以上就代表有意義;  其他的endpoint 包括 other cognitive outcomes, evaluation of the incidence, location of brain metastases, and overall survival.

結果發現在PCI with hippocampus avoidance並不會改善認知功能, 在兩年的時候, 腦轉移的情形在兩組差不多!

=> 細讀會發現, 一篇PCI with hippocampus avoidance可以改善認知功能, 另一篇則不行, 因此臨床上目前針對SCLC, 做PCI 是否要使用hippocampus avoidance, 還是一個有爭議的主題!

=> 目前有第三篇進行中的研究, NRG-CC003, 期待發表的結果可以讓這個主題形成共識!

Reference:

1. Rodríguez de Dios N, Couñago F, Murcia-Mejía M, et al. Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study. J Clin Oncol. 2021;39(28):3118-3127.

2. Belderbos JSA, De Ruysscher DKM, De Jaeger K, et al. Phase 3 Randomized Trial of Prophylactic Cranial Irradiation With or Without Hippocampus Avoidance in SCLC (NCT01780675). J Thorac Oncol. 2021;16(5):840-849. doi:10.1016/j.jtho.2020.12.024

3. NRG Oncology CC003: A randomized phase II/III trial of prophylactic cranial irradiation with or without hippocampal avoidance for small cell lung cancer.