COPD予後指標 BARC

Predicting COPD 1-year mortality using prognostic predictors routinely measured in primary care
C. I. Bloom ,et al.
BMC Medicine201917:73
https://doi.org/10.1186/s12916-019-1310-0


54990名の被検者　UK電子カルテ使用プライマリケアCOPDコホート
初期コホート トレーニングとtest setへ均等ランダム化割り付け
外部データは2つめのコホート
12ヶ月死亡率推定リスクモデルCox回帰でbackwards elimination使用トレーニングセット

BMI、血液検査(B)、年齢(A)、呼吸変数（気道閉塞、急性増悪）(R)、併存症使用(C)を含む80の変数

具体的には・・・

FEV1, GOLD staging (FEV1 and FVC), C-reactive protein (CRP), albumin (low = < 35 g/L), haemoglobin, fibrinogen, platelets (low = < 150 × 109/L, high = > 400 × 109/L) and creatinine; creatinine above 120 μmol/L for males, or 110 μmol/L for females, was used to define chronic kidney disease (CKD). BMI was measured as kg/m2 (underweight < 19, normal = 19–25, overweight = 25–30, obese ≥ 30). Exacerbations, treated within primary (labelled as moderate) or secondary care (labelled as severe)

BODEx、DOSE、ADOと比較

リスクモデルでパフォーマンス推定

acceptable predictive performance

 (test set: C-index = 0.79, 95% CI 0.78–0.81, D-statistic = 1.87, 95% CI 1.77–1.96, calibration slope = 0.95, 95% CI 0.9–0.99; external dataset: C-index = 0.67, 95% CI 0.65–0.7, D-statistic = 0.98, 95% CI 0.8–1.2, calibration slope = 0.54, 95% CI 0.45–0.64)

acceptable accuracy predicting the probability of death

(probability of death in 1 year, n high-risk group, test set: expected = 0.31, observed = 0.30; external dataset: expected = 0.22, observed = 0.27)

BARCは既存の指数スコアよりspecialist respiratory variableなしでは優れている　

(area under the curve: BARC = 0.78, 95% CI 0.76–0.79; BODEx = 0.48, 95% CI 0.45–0.51; DOSE = 0.60, 95% CI 0.57–0.61; ADO = 0.68, 95% CI 0.66–0.69, external dataset: BARC = 0.70, 95% CI 0.67–0.72; BODEx = 0.41, 95% CI 0.38–0.45; DOSE = 0.52, 95% CI 0.49–0.55; ADO = 0.57, 95% CI 0.54–0.60)

転移性直腸結腸癌治療患者における高用量ビタミンDの効果

サプリメントにとってポジティブな話が一部あるが

・ビタミンD中毒の危険性配慮必要

・がん治療中の特殊な状況下での評価

これを忘れてはいけない

2つの報告を列挙

後者の報告で一部肯定的内容あり

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ビタミンDサプリメントは消化器系がん患者において生存率を改善するか？

ランダム化臨床トライアル、417名の消化器系がん（食道〜直腸）患者において、5年再発なし生存率をビタミンD 2000 IU/日 vs プラシーボ比較し、 77% vs 69％　統計学的有意さ認めず

意義：ビタミンDサプリメントは消化器系がんの無再発生存率改善せず 

Effect of Vitamin D Supplementation on Relapse-Free Survival Among Patients With Digestive Tract Cancers: The AMATERASU Randomized Clinical Trial  Mitsuyoshi Urashima, MD; Hironori Ohdaira, MD; Taisuke Akutsu, MD; et al Earn CME creditEditorial: Insights From 2 New Trials on Vitamin D as Cancer Therapy; Elizabeth L. Barry, PhD; Michael N. Passarelli, PhD; John A. Baron, MD, MS, MSc

高用量ビタミンD3サプリメントは、進行・転移性直腸結腸癌患者における標準化学療法に追加したとき、無進行生存率延長するか？

第2相ランダム化トライアル、進行あるいは転移性直腸結腸癌患者139名にて、化学療法＋大量ビタミンD3サプリメント vs 化学療法＋標準量ビタミンD3にて、無進行生存期間 13ヶ月 vs 11ヶ月で、統計学的有意差なしだが、無進行生存・死亡に関する多変量ハザード比は0.64と統計学的に有意。

意義：進行・転移性直腸結腸癌患者における高用量ビタミンD3サプリメントにpotentialがあるかもしれない。大規模多施設RCT評価必要

Effect of High-Dose vs Standard-Dose Vitamin D₃Supplementation on Progression-Free Survival Among Patients With Advanced or Metastatic Colorectal Cancer: The SUNSHINE Randomized Clinical Trial   

Kimmie Ng, MD, MPH; Halla S. Nimeiri, MD; Nadine J. McCleary, MD, MPH; et al 

Editorial: Insights From 2 New Trials on Vitamin D as Cancer Therapy; Elizabeth L. Barry, PhD; Michael N. Passarelli, PhD; John A. Baron, MD, MS, MSc

a double-blind, multicenter, phase 2 randomized clinical trial called SUNSHINE was conducted to test whether vitamin D3 supplementation to raise plasma 25-hydroxyvitamin D levels can improve outcomes in patients with advanced or metastatic colorectal cancer. 

mFOLFOX6 療 法＋ ベバシズマブ（Bevacizumab）は、血管内皮細胞増殖因子（VEGF）に対するモノクローナル抗体療法ベース

All patients received chemotherapy with a continuous infusion of 2400 mg/m2 of 5-fluorouracil (5-FU) over 46 to 48 hours, a bolus of 400 mg/m2 of 5-FU, 400 mg/m2 of leucovorin, and 85 mg/m2 of oxaliplatin (mFOLFOX6) plus 5 mg/kg of bevacizumab administered intravenously every 14 days per institutional standard of care (1 cycle = 14 days). Bevacizumab was allowed to be omitted during the first cycle and started with cycle 2 at the investigator’s discretion. 

Patients were randomized by a statistician (H.Z.) using computerized block randomization with a block size of 2 in a 1:1 ratio to concurrent high-dose vs standard-dose oral vitamin D3. The high-dose group received a loading dose of 8000 IU/d of vitamin D3 (two 4000 IU capsules) for cycle 1 followed by 4000 IU/d for subsequent cycles. 

The standard-dose group received 400 IU/d of vitamin D3 during all cycles (one 400 IU capsule plus 1 placebo capsule during cycle 1 to maintain blinding).

 Adherence to vitamin D3 was monitored using drug diaries and pill counts. Participants continued to receive treatment until disease progression, intolerable toxicity, or decision to discontinue treatment.