降低骨相關(guān)事件

1、充分發(fā)揮護(hù)理在降低骨相關(guān)事件中的作用,Chen MinDirector for Department of oncology nurse , Central Hospital,FuLing,ChongQing Cityl,,,骨相關(guān)事件類型Types of Skeletal-Related Events,病理性骨折,SREs,外科干預(yù),需要放療,高鈣血癥,脊髓壓迫,骨轉(zhuǎn)移流行病學(xué)：問題嚴(yán)重性Bone Metastases

2、Epidemiology: Scope of the Problem,美國每年影響 > 400,000個人 [1]Greater than any other site of tumor metastasis,1. Coleman RE, et al. Cancer Treat Rev. 2010;36:615-620. 2. Kyle RA, et al. Mayo Clin Proc. 2003;78:21-33. 3. C

3、oleman RE. Oncologist. 2004;9(suppl 4):14-27. 4. Palumbo A, et al. Blood. 2004;104:3052-3057. 5. Smith W, et al. Semin Oncol. 2004;31(2 suppl 4):11-15. 6. Lipton A. J Support Oncol. 2004;2:205-213. 7. Tu SM, et al. Cance

4、r Treat Res. 2004;118:23-46.,,骨轉(zhuǎn)移：詳情Bone Metastasis: Details,轉(zhuǎn)移常常發(fā)生于中軸骨骼紅骨髓位點循環(huán)量大,流速低骨基質(zhì)促進(jìn)腫瘤細(xì)胞侵入腫瘤細(xì)胞產(chǎn)生粘附分子有助腫瘤細(xì)胞附著,骨轉(zhuǎn)移發(fā)生的病理生理學(xué)Pathophysiology of the Development of Bone Metastases,骨重塑過程：終身持續(xù)[1]，兩種細(xì)胞的活性是由骨微環(huán)境中的激素和生

5、長因子調(diào)節(jié)[1],1. Roodman GD. N Engl J Med. 2004;350:1655-1664. 2. Kodama H, et al. J Exp Med. 1991;173:1291-1294. 3. Lacey DL, et al. Cell. 1998;93:165-176. 4. Simonet WS, et al. Cell. 1997;89:309-319.,覆蓋作用Frost’s Contribut

6、ion,破骨細(xì)胞重吸收,新骨形成,,,,,,,,,,,,,,,,,,,,,Hattner R, et al. Nature. 1965:206:489-490.,異常骨重塑導(dǎo)致骨質(zhì)疏松Abnormal Bone Remodeling Leads to Osteoporosis,Osteoporosis,,破骨組織再吸收,成骨細(xì)胞的新骨形成,勝于,,,,,,,,,,,,,,,,,,,,,,骨,RANK,RANKL配體,,,骨再吸收,破骨

7、細(xì)胞,骨腫瘤細(xì)胞,生長因子 (TGF-ß, IGFs, FGFs, PDGFs, BMPs),細(xì)胞因子和生長因子(IL-6, IL-8, IL-1ß, PGE-2, TNF-α, CSF-1, PTHrP),,,,,,,,Adapted from Roodman GD. N Engl J Med. 2004;350:1655-1664.,,,,,,,,,RANKL,RANKL,,,對腫瘤的直接效應(yīng)?,,,成骨細(xì)胞,

8、RANK 配體是骨組織破壞“惡性循環(huán)”的關(guān)鍵介導(dǎo)子Ligand Is a Key Mediator in the “Vicious Cycle” of Bone Destruction,,骨轉(zhuǎn)移的類型Types of Bone Metastasis,骨轉(zhuǎn)移的類型Types of Bone Metastasis,溶骨性轉(zhuǎn)移,成骨性轉(zhuǎn)移,Lipton A. J Support Oncol. 2004;2:205-220.,,,,,腫

9、瘤導(dǎo)致的溶骨性破壞,骨轉(zhuǎn)移的后果Morbidity From Bone Metastases,,臨床評估確定骨健康Clinical Evaluation to Assess Bone Health Health,體格檢查應(yīng)該全面，不能只局限于骨骼系統(tǒng)實驗室檢查應(yīng)全面而系統(tǒng),Saylor PJ, et al. Prostate Cancer Prostatic Dis. 2010;13:20-27.Gralow JR, et al

10、. J Natl Compr Canc Netw. 2009;7(suppl 3):S1-S32.,骨相關(guān)事件風(fēng)險Risk of Skeletal-Related Events,骨相關(guān)事件發(fā)生率年骨折發(fā)生率為 20% 到30%未經(jīng)雙磷類藥物治療者平均每3-6月發(fā)生一次明顯的骨并發(fā)癥,骨并發(fā)癥,脊髓壓迫,骨外科,高血鈣HCM,骨折,骨放療,0,10,20,30,40,50,患者 (%),其他前列腺癌骨髓瘤乳腺癌,,,,,Rep

11、roduced and adapted with permission from the American Association for Cancer Research. Coleman RE. Clin Cancer Res. 2006;12:6243s-6249s.,骨轉(zhuǎn)移主要治療選擇Primary Treatment Options for Bone Metastases,雙膦酸鹽的作用機制,,,,,,,,,,,,,,,,,,

12、,,,,,,,,,,,,,,,,,,,,,,,,,,,抑制破骨細(xì)胞形成分化成熟和活性，促進(jìn)其凋亡,骨吸收過程中局部釋放,成骨細(xì)胞和破骨細(xì)胞活動時濃度增加,調(diào)制成骨細(xì)胞和破骨細(xì)胞之間信號傳遞,骨修正劑Bone-Modifying Agents,雙磷酸鹽NF-kB(RANK) 活化因子配體抑制因子 Denosomab,III 期研究:芳香酶抑制劑治療早期乳腺癌期間加用戴諾單抗的療效,在美國和加拿大進(jìn)行多中心、隨機 、雙盲、安慰劑

13、對照研究,,接受芳香酶抑制劑治療的ER+的乳腺癌患者(N = 252),Ellis GK, et al. J Clin Oncol. 2008;26:4875-4882.,Denosumab 60 mg SC q6m x 4 (n = 127),Placebo SC q6m x 4 (n = 125),,,Ellis GK, et al. J Clin Oncol. 2008:26:4875-4882. Reprinted with

14、 permission. © 2008 American Society of Clinical Oncology. All rights reserved.,,*P < .0001 vs placebo.,,Change (± 95% CI) From Baseline in L-Spine BMD (%),8,6,4,2,0,-2,7,5,3,1,-1,-3,*,*,*,*,*,,,,,,,1,3,6,1

15、2,24,5.5% differenceat Mo 12,Denosumab (n = 123),Placebo (n = 122),,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,7.6% differenceat Mo 24,Mos,,Effect of Denosumab on Lumbar Spine Bone Mineral Density,,Denosumab [package insert].,

16、治療效果： Denosumab Treatment Effect: Denosumab,2011指南更新內(nèi)容 2011 Updates to Clinical Practice Guidelines,1. Van Poznak C, et al. J Clin Oncol. 29:1221-1227. 2. NCCN. Clinical practice guidelines in oncology: breast cancer.

17、v.2.2011. 3. NCCN. Clinical practice guidelines in oncology: prostate cancer. v.1.2011.,小結(jié)(Summary),尸解分析提示：腫瘤致死的患者70%具有骨轉(zhuǎn)移 最常見于乳腺癌、前列腺癌、腎癌和肺癌治療骨轉(zhuǎn)移是近16年發(fā)展起來的，主要是為了降低 SREs,護(hù)理思考Putting It All Together:Overall Nursing Co

18、nsiderations,腫瘤護(hù)理是患者治療有效的關(guān)鍵Oncology Nurses Are Central to Effective Patient Management,患者教育：骨健康Patient Education: Bone Health,腫瘤轉(zhuǎn)移所致的骨痛Causes of Bone Pain in Metastatic Cancer,疼痛病因骨腫瘤、骨折 炎癥介質(zhì)骨內(nèi)壓增加疼痛類型間斷的，慢性的，爆發(fā)性

19、，偶然性,評估定位（Location）定性（性質(zhì)Quality ）相關(guān)的癥狀A(yù)ssociated symptoms時間Time強度Intensity/持續(xù)時間duration,Faiman B. Cleve Clin J Med. 2010;77:273-278.Siemionow K, et al. Cleve Clin J Med. 2008;75:557-566.,,0,,10,Least to Worst,0

20、,輕 to 重,10,,WHO的三階梯藥物治療World Health Organization Medical Management,,,,,,1 級輕度疼痛 (1-4),2級中度疼痛(5-7),3級 重度疼痛 (8-10),嗎啡二氫嗎啡酮美沙酮芬太尼羥考酮±輔助劑,阿司匹林/可待因阿司匹林/羥考酮曲馬多±輔助劑,阿司匹林撲熱息痛NSAIDs± 輔助劑,Christo PJ, et

21、 al. Ann NY Acad Sci. 2008;1138:278-298.Adapted from WHO’s pain ladder. Available at: http://www.who.int/cancer/palliative/painladder/en/.,,,,骨健康：精心計劃Bone Health: Care Plan,確定部位和骨折病因 X-ray, CT scan, or MRI骨掃描Bone sca

22、n, 骨測定bone survey (MM)疼痛控制 藥物治療:阿片制劑(opiates)有否放化療指征?病變位點, 疾病進(jìn)展范圍、疼痛范圍和程度雙磷酸鹽或 denosumab治療的時間,死亡率增加,,脊柱壓縮性骨折級聯(lián)Vertebral Compression Fracture Cascade,腫瘤患者鈣補充Calcium Supplementation in Cancer,雙磷酸鹽和RANKL抑制劑可致低血鈣骨重建

23、必須物質(zhì)美國骨質(zhì)疏松協(xié)會推薦≥50歲: 每天總量1200mg鈣和800-1000IU維生素D攝入檢查血鈣和維生素D水平骨密度基線評估和風(fēng)險度監(jiān)測蛋白、咖啡，質(zhì)子泵抑制劑飲食含鈣,檸檬酸鈣,雙膦酸鹽和Denosumab,對骨轉(zhuǎn)移患者有效?？谱o(hù)理（Specific nursing）要關(guān)注雙磷酸鹽和denosumab的應(yīng)用指征和使用觀察,雙磷酸鹽和Denosumab的副反應(yīng)Bisphosphonates and Novel A

24、gents: Adverse Effects,雙磷酸鹽相關(guān)的腎臟毒性Bisphosphonate-Associated Renal Toxicity,包括水腫、尿頻、血尿、腎功能衰竭Cr升高范圍從無癥狀到透析依賴唑來磷酸的劑量要根據(jù)Cr清除率確定,Zoledronic acid [package insert]. 2011. Kyle et al, J Clin Oncol. 2007;25:2464-2472. Tanvetya

25、non T, et al. Ann Oncol. 2006;17:897-907.,,雙磷酸相關(guān)腎臟毒性Bisphosphonate-Associated Renal Toxicity,停藥指征：Cr清除率< 30 mL/min Cr值從正常上升≥ 0.5mg/dL Cr從異常基線上升≥ 1.0mg/dL 等到Cr降到基線值10%以內(nèi)才能再次用藥,Kyle RA, et al. J Clin Oncol. 2007;25

26、:2464-2472.,雙磷酸鹽和戴諾單抗：骨壞死Bisphosphonates and Denosumab: Osteonecrosis,2004 國際網(wǎng)絡(luò)調(diào)查顯示 唑來磷酸的發(fā)生率是10%,帕米磷酸二鈉的發(fā)生率是4% 頜骨壞死可能與應(yīng)用雙磷酸鹽的持續(xù)時間相關(guān)當(dāng)牙齒或頜骨出現(xiàn)疼痛或骨外露，要高度懷疑頜骨壞死,Aapro M, et al. Oncologist. 2010;15:1147-1158. Durie BG, et

27、al. N Engl J Med. 2005;353:99-102. Zervas K, et al. Br J Haematol. 2006;134:620-623.,防止牙壞死的指南Guidelines for the Prevention of ONJ,在接受任何雙磷酸鹽治療前患者應(yīng)該進(jìn)行全面的牙齒評估和適當(dāng)牙齒預(yù)防,Aapro M, et al. Oncologist. 2010;15:1147-1158. Kyle RA,