Diffuse large B cell lymphoma in elderly patients(>80 years old) British Journal of Haematology, 2012, 157, 159–170 Annals of Oncology 23: 1280–1286, 2012 R4 簡聖軒 指導老師: 蕭樑材大夫 Characteristic in elderly patient Evaluation of elderly patient Prognostic factor Treatment strategy 圖1. 歷年0歲平均餘命及死亡率 0歲平均餘命 (歲) 100年國人零歲平均餘命,男性為76.0歲,女性為82.7歲 每十萬人口 死亡率 80 79.2 79.2 9 810.2 76 74.5 72.0 655.5 72 625.3 647.7 6 68 554.6 462.4 479.7 455.6 64 60 3 70 71 72 73 74 75 76 77 78 79 80 平均餘命 81 82 83 84 85 86 粗死亡率 87 88 89 90 91 92 標準化死亡率 93 94 95 96 97 98 99 100年 圖2.死亡人數年齡結構比 100% 100年65歲以上死亡數占全體死亡數之68.5% 12.9 25.7 37.2 38.3 80% 34.0 60% 38.8 31.3 30.2 40% 53.1 20% 35.5 31.5 31.5 0% 70 71 72 73 74 75 76 77 78 79 80 0-64 歲 81 82 83 84 85 86 65-79 歲 87 88 89 90 91 92 80 歲以上 93 94 95 96 97 98 99 100年 公開類 年 報 編製機關 每年終了第3年4月底前填報 表 號 行政院衛生署國民健康局 1631-08-01 十大惡性腫瘤申報發生人數及發生率 中華民國 97 年 總 順 位 國際疾病分類 腫瘤學代碼 ICD-O-3 計 男 發生率 部 位 發生人數 (每10萬人口) (C00~C80) 單位:人 國際疾病分類腫 瘤學代碼ICD-O3 性 女 發生率 部 位 發生人數 國際疾病分 類腫瘤學代 碼ICD-O-3 性 發生率 部 位 發生人數 (每10萬人 (C00~C80) 口) (C00~C80) (每10萬人 口) C22 肝及肝內 膽管 7,401 63.66 C50 女性乳房 8,136 71.30 47.77 C18-C21 結腸及直 腸 6,277 53.99 C18-C21 結腸及直 腸 4,727 41.43 10,565 45.86 C33,C34 肺、支氣 管及氣管 6,194 53.28 C33,C34 肺、支氣 管及氣管 3,322 29.11 肺、支氣 管及氣管 9,516 41.31 C00-C06,C09, C10,C12-C14 口腔、口 咽及下咽 5,349 46.01 C22 肝及肝內 膽管 3,164 27.73 攝護腺 3,603 30.99 (2) C61 攝護腺 3,603 30.99 C53 子宮頸 1,725 15.12 口腔、口 咽及下咽 5,781 25.09 C16 胃 2,303 19.81 C73 甲狀腺 1,561 13.68 C16 胃 3,578 15.53 C15 食道 1,849 15.90 C54 子宮體 1,424 12.48 8 C53 子宮頸 1,725 15.12 (1) C67 膀胱 1,476 12.70 C16 胃 1,275 11.17 9 C54 子宮體 1,424 12.48 (1) C44 皮膚 1,380 11.87 C44 皮膚 1,205 10.56 10 C44 皮膚 2,585 11.22 C11 鼻咽 1,162 9.99 卵巢、輸 卵管及寬 韌帶 1,110 9.73 45,171 388.52 34,647 303.64 1 C50 女性乳房 8,136 2 C18-C21 結腸及直 腸 11,004 3 C22 肝及肝內 膽管 4 C33,C34 5 C61 6 C00-C06,C09, C10,C12-C14 7 全癌症 79,818 71.30 (1) 346.48 全癌症 C56,C57.0C57.4 全癌症 公開類 年 報 編製機關 每年終了第3年4月底前填報 表 行政院衛生署國民健康局 號 1631-08-01 十大惡性腫瘤申報發生人數及發生率 中華民國 總 順 位 國際疾病分類 腫瘤學代碼 ICD-O-3 位 發生人數 (每10萬人口) (C00~C80) 女性乳房 單位:人 男 發生率 部 98 年 計 國際疾病分類 腫瘤學代碼 ICD-O-3 性 女 發生率 部 位 發生人數 (C00~C80) 國際疾病分類 腫瘤學代碼 ICD-O-3 (每10萬人口) (C00~C80) C22 肝及肝內膽 管 7,747 66.57 C50 54.01 C18-C21 結腸及直腸 7,151 61.45 11,080 47.92 C33,C34 肺、支氣管 及氣管 6,737 10,643 46.03 C00-C06,C09, C10,C12-C14 口腔、口咽 及下咽 1 C50 2 C18-C21 結腸及直腸 12,488 3 C22 肝及肝內膽 管 4 C33,C34 肺、支氣管 及氣管 5 C61 6 C00-C06,C09, C10,C12-C14 7 8,926 77.73 (1) 性 發生率 部 位 發生人數 (每10萬人口) 女性乳房 8,926 77.73 C18-C21 結腸及直腸 5,337 46.48 57.89 C33,C34 肺、支氣管 及氣管 3,906 34.02 5,927 50.93 C22 肝及肝內膽 管 3,333 29.03 攝護腺 4,013 34.49 (2) C61 攝護腺 4,013 34.49 C73 甲狀腺 1,846 16.08 口腔、口咽 及下咽 6,480 28.03 C16 胃 2,404 20.66 C53 子宮頸 1,796 15.64 C16 胃 3,848 16.64 C15 食道 1,898 16.31 C54 子宮體 1,496 13.03 8 C53 子宮頸 1,796 15.64 (1) C44 皮膚 1,589 13.66 C16 胃 1,444 12.58 9 C54 子宮體 1,496 13.03 (1) C67 膀胱 1,419 12.19 C44 皮膚 1,339 11.66 10 C44 皮膚 2,928 12.66 非何杰金氏 淋巴瘤 1,205 10.36 C56,C57.0-C57.4 卵巢、輸卵 管及寬韌帶 1,113 9.69 87,189 377.12 49,022 ######## 38,167 ######## 全癌症 M959-976 全癌症 全癌症 Multiple co-morbid illness Decreased portal/renal perfusion flow Altered pharmacokinetics Decreased bone marrow hematopioetic reserve Poor compliance and tolerance Exclude in clinical trial, no available guideline NHL 3 hematology centers Israel 1984-2004 age 80 years or older at diagnosis. Annals of Oncology 17: 928–934, 2006 Annals of Oncology 17: 928–934, 2006 Annals of Oncology 17: 928–934, 2006 Aggressive lymphoma increase with age, especially in patient age > 85 years Complete response : 50 %, In aggressive lymphoma, short survival median survival : 18 months 3 year survival rate: 35% Prognostic parameter: IPI and PS Aggressive chemotherapy had a significantly longer median survival than no or mild therapy For with aggressive lymphoma, age alone should not be a contraindication for treatment Five regional Dutch cancer registries From 1997-2004 (N:419) After adjustment other variable, age and performance was independently associated with receiving CHOP like chemotherapy Grade 3-4 toxicity occurred in 67 % in CHOP like therapy , 40 % in milder regimen Age 75-79 80-85 >85 Toxicity 62% 73% 85 % Tx >6 CHOP like <6CHOP like Sub-optiamal CR 67 29 11 Recurrence 38 33 63 Mean time from diagnosis to recurence 20 months 16 months 16 Tx >6 CHOP like <6CHOP like Suboptiamal Nil 5 yr survivial 38 22 12 4 After correction aaIPI, The effect of therapy (in four subgroups) was independently associated with survival N Engl J Med 2002; 346:235-242 60 - 80 years of age with diffise large B cell lymphoma , randomization mainly in France stage II, III, or IV disease ECOG of 0 to 2 (good to fair) No history of indolent lymphoma central nervous system involvement, active cancer Excluded if cardiac contraindication to doxorubicin therapy Excluded neurologic contraindication to vincristine G-CSF in grade 4 neutropenia C+H decreased 50 % in > 2 x grade 4 neutropenia C+H decreased 50 % Grade 3- 4 thrombocytopenia If neutrophil < 1500 or platelet < 10000, hold Tx If hold Tx > 2 wks, DC treatment plan The doses of rituximab were not modified, but rituximab was discontinued when CHOP was stopped. Treatment was stopped if lymphoma progressed Lancet Oncol 2011; 12: 460–68 Prospective, multicentre, single-arm, phase 2 study GELA ran the study in 38 centers in France and Belgium Age > 80 years with diffuse large B-cell lymphoma. ECOG< 2 Rituximab + CHOP (R-miniCHOP) at 3-week intervals. 375 mg/m2 rituximab, 400 mg/m2 cyclophosphamide, 25 mg/m2 doxorubicin, 1 mg vincristine 40 mg/m2 prednisone on days 1–5. G-CSF or erythropoietin support was left to the discretion of the treating physician. Recommend G-CSF SC used on day 6-day13 if severe neutropenic fever until neutrophil >1000 Hold theray if neutrophil < 1000, if neutophil still < 1000 for more than 28 days, treatment DC 108/149 complete 6 X R-miniCHOP Median survival was 21 months 2 year prgoression free survival 47% 58 death report: 33 lymphoma progression 12 toxicities of treatment Most frequently side effeict : hematological toxicity >3 grade neutropenia : 59 Febrile neutropenia : 11 Median overall survival was 29 months 29 months median survival 62% complete response rate (CR+uCR) The only parameter associated with poor outcome is low serum albumin Death from toxicity in previous study: 9%-23%, but 5 death in first cycle in this study Despite absence of a control arm. This study suggest selected patient older than 80 years with DLBCL in good performance, R-miniCHOP is considered Treatment in very elderly patient is no more rare pratice As age increased, aggressive lymphoma is more popular Adequate evaluation is essential for treatment decision, suitable for elderly tool Performance, LDH, albumin are most import prognostic factor Age would not be contraindication for therapy Median survival: 18-20 months and complete response: 50 % in treatment population Treatment with Rituximab and reduced dose of chemotherapy would be acceptable strategy Thanks