1. Diffuse large B cell lymphoma in elderly patients(>80 years old)
Journal reading
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

2. Outline Characteristic in elderly patient
Evaluation of elderly patient
Prognostic factor
Treatment strategy

3. 100年國人零歲平均餘命，男性為76.0歲，女性為82.7歲

4. 100年65歲以上死亡數占全體死亡數之68.5%

5. 十大惡性腫瘤申報發生人數及發生率 公開類 年 報 每年終了第3年4月底前填報 1631-08-01 中華民國 97 年 順 位 總 計
編製機關
行政院衛生署國民健康局
年　報
每年終了第3年4月底前填報
表　　號
十大惡性腫瘤申報發生人數及發生率
中華民國　97 年
單位：人
順　位
總　　　　　　　　　　　　計
男　　　　　　　　　　　　性
女　　　　　　　　　　　　性
國際疾病分類腫瘤學代碼ICD-O-3
部　位
發生人數
發生率
(C00～C80)
(每10萬人口) 1
C50
女性乳房
8,136
71.30
(1)
C22
肝及肝內膽管
7,401
63.66 2
C18-C21
結腸及直腸
11,004
47.77
6,277
53.99
4,727
41.43 3
10,565
45.86
C33,C34
肺、支氣管及氣管
6,194
53.28
3,322
29.11 4
9,516
41.31
C00-C06,C09, C10,C12-C14
口腔、口咽及下咽
5,349
46.01
3,164
27.73 5
C61
攝護腺
3,603
30.99
(2)
C53
子宮頸
1,725
15.12 6
5,781
25.09
C16 胃
2,303
19.81
C73
甲狀腺
1,561
13.68 7
3,578
15.53
C15 食道
1,849
15.90
C54
子宮體
1,424
12.48 8
C67 膀胱
1,476
12.70
1,275
11.17 9
C44 皮膚
1,380
11.87
1,205
10.56 10
2,585
11.22
C11 鼻咽
1,162
9.99
C56,C57.0-C57.4
卵巢、輸卵管及寬韌帶
1,110
9.73
全癌症
79,818
346.48
45,171
388.52
34,647
303.64

6. 十大惡性腫瘤申報發生人數及發生率 公開類 年 報 每年終了第3年4月底前填報 1631-08-01 中華民國 98 年 順 位 總 計
編製機關
行政院衛生署國民健康局
年　報
每年終了第3年4月底前填報
表　　號
十大惡性腫瘤申報發生人數及發生率
中華民國　98 年
單位：人
順　位
總　　　　　　　　　　　　計
男　　　　　　　　　　　　性
女　　　　　　　　　　　　性
國際疾病分類腫瘤學代碼ICD-O-3
部　位
發生人數
發生率
(C00～C80)
(每10萬人口) 1
C50
女性乳房
8,926
77.73
(1)
C22
肝及肝內膽管
7,747
66.57 2
C18-C21
結腸及直腸
12,488
54.01
7,151
61.45
5,337
46.48 3
11,080
47.92
C33,C34
肺、支氣管及氣管
6,737
57.89
3,906
34.02 4
10,643
46.03
C00-C06,C09, C10,C12-C14
口腔、口咽及下咽
5,927
50.93
3,333
29.03 5
C61
攝護腺
4,013
34.49
(2)
C73
甲狀腺
1,846
16.08 6
6,480
28.03
C16 胃
2,404
20.66
C53
子宮頸
1,796
15.64 7
3,848
16.64
C15 食道
1,898
16.31
C54
子宮體
1,496
13.03 8
C44 皮膚
1,589
13.66
1,444
12.58 9
C67 膀胱
1,419
12.19
1,339
11.66 10
2,928
12.66 M
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
全癌症
87,189
377.12
49,022
########
38,167

7. Difficult in treatment
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

8. Evaluation-cumulative illness score

9. Charlson score

10. IPI/AA-IPI,/R-IPI,/E-IPI

11. NHL 3 hematology centers
Israel
age 80 years or older at diagnosis.

12. Annals of Oncology 17: 928–934, 2006

13. Annals of Oncology 17: 928–934, 2006

14. Annals of Oncology 17: 928–934, 2006

17. Discussion
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%

18. Discussion 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

19. Five regional Dutch cancer registries
From (N:419)

21. After adjustment other variable, age and performance was independently associated with receiving CHOP like chemotherapy

22. Toxicities and response
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 %
CHOP-like chemotherapy was coded as CHOP, CHOP + rituximab
(RCHOP), cyclophosphamide + hydroxorubicin + Vm-26 + prednisone +
bleomycin + vincristine, and CHOP + methotrexate 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

23. Survival Tx >6 CHOP like <6CHOP like Sub-optiamal Nil
5 yr survivial 38 22 12 4

24. Influence survival
After correction aaIPI, The effect of therapy (in four subgroups) was independently associated with survival

25. N Engl J Med 2002; 346:

26. R-CHOP VS CHOP in elderly
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
Patients treated with CHOP received the combination of 750 mg of cyclophosphamide per square meter of body-surface area on day 1; 50 mg of doxorubicin per square meter on day 1; 1.4 mg of vincristine per square meter, up to a maximal dose of 2 mg, on day 1; and 40 mg of prednisone per square meter per day for five days. They were treated every three weeks for eight cycles of CHOP. Patients treated with CHOP plus rituximab also received rituximab, at a dose of 375 mg per square meter, on day 1 of each of the eight cycles of CHOP. The rituximab infusion was interrupted in the event of fever, chills, edema, congestion of the head and neck mucosa, hypotension, or any other serious adverse event and was resumed when such an event was no longer occurring. No radiation therapy was scheduled or recommended at the end of treatment.

27. R-CHOP VS CHOP in elderly
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

29. Lancet Oncol 2011; 12: 460–68

30. Procedure 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.
Inclusion criteria were Ann
Arbor stage I bulky to stage IV disease; age-adjusted
international prognostic index (IPI)18 score of 1, 2, or 3
(based on disease stage, performance status, and lactate
dehydrogenase concentration; a score of 2–3 suggests a
higher risk of death than a score of 0–1); Eastern
Cooperative Oncology Group (ECOG) performance status
score of 2 or less;19 minimum life expectancy of 3 months;
and negative HIV, hepatitis B virus, and hepatitis C virus
serology test 4 weeks or less before enrolment (except
after vaccination).
Exclusion criteria were any other lymphoma subtype;
history of treated or non-treated indolent lymphoma; CNS
or meningeal involvement; contraindication to any drug
in the chemotherapy regimen; serious active disease
according to the investigator’s decision; poor renal
function, defi ned as creatinine concentration greater than
150 μmol/L; poor hepatic function, defi ned as total
bilirubin concentration greater than 30 μmol/L or
transaminases over 2・5 times the maximum normal
concentration, unless these abnormalities were related to
the lymphoma; poor bone-marrow reserve, defi ned as
neutrophil count less than 1・5×10⁹/L or platelet count less
than 100×10⁹/L, unless caused by bone-marrow
infi ltration; history of cancer during the past 5 years, with
the exception of non-melanoma skin tumours or stage 0
(in situ) cervical carcinoma; treatment with any
investigational drug within 30 days before the planned

31. 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

33. Association of deaths with treatment during treatment phase

34. Response 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

35. Median overall survival was 29 months

38. Conclusion 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

39. Take home message
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

40. Take home message Age would not be contraindication for therapy
Median survival: months and complete response: 50 % in treatment population
Treatment with Rituximab and reduced dose of chemotherapy would be acceptable strategy

41. Thanks