肺癌の病期分類（TNM分類第8版）

出典
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1: 著者提供

治療方針の決定（臨床病期I期）

臨床病期I期（TNM分類第8版）
 
①標準的根治切除が行われた場合：
  1. 臨床病期IA1、IA2：手術単独
  1. 臨床病期IA3、IB：術後にUFT内服を行うよう勧められる
②標準的根治切除が不可能な場合（あるいは拒否）：
  1. 放射線単独療法あるいは縮小手術を検討する
 
参考文献：
  1. 日本肺癌学会編：肺癌診療ガイドライン2023年版
  1. Kato H, Ichinose Y, Ohta M, et al.：A randomized trial of adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung. N Engl J Med. 2004 Apr 22;350(17):1713-21. PMID：15102997
  1. Hamada C, Tanaka F, Ohta M, et al.：Meta-analysis of postoperative adjuvant chemotherapy with tegafur-uracil in non-small-cell lung cancer. J Clin Oncol. 2005 Aug 1;23(22):4999-5006. PMID：16051951
  1. Hamada C, Tsuboi M, Ohta M, et al.：Effect of postoperative adjuvant chemotherapy with tegafur-uracil on survival in patients with stage IA non-small cell lung cancer: an exploratory analysis from a meta-analysis of six randomized controlled trials. J Thorac Oncol. 2009 Dec;4(12):1511-6. PMID：19875974
  1. Saji H, Okada M, Tsuboi M, et al.: Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer (JCOG0802/WJOG4607L): a multicentre, open-label, phase 3, randomized, controlled, non-inferiority trial. Lancet. 2022 Apr 23;399(10335):1607-1617. PMID:35461558

治療方針の決定（臨床病期II期）

臨床病期II期（TNM分類第8版）
 
①標準的根治切除が行われた場合：
  1. 臨床病期IIA：術後にUFT内服を行うよう勧められる
  1. 臨床病期IIB：術前に薬物療法（プラチナ併用化学療法）を検討する
  1. 術後に薬物療法（プラチナ併用化学療法）を行うよう勧められる
  1. 術後に薬物療法（プラチナ併用化学療法＋アテゾリズマブ）を検討する
  1. 臨床病期II（EGFR遺伝子変異/ALK融合遺伝子陰性）：術前に薬物療法（プラチナ併用化学療法＋ニボルマブ）を検討する
  1. 臨床病期II（EGFR遺伝子変異）：術後に薬物療法（プラチナ併用化学療法＋オシメルチニブ）を検討する
②標準的根治切除が不可能な場合（あるいは拒否）：
  1. 放射線療法（可能であれば化学放射線療法）を行うよう勧められる
 
参考文献：
  1. 日本肺癌学会編：肺癌診療ガイドライン2023年版
  1. Douillard JY, Rosell R, De Lena, et al.: Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial. Lancet Oncol. 2006 Sep;7(9):719-27. PMID：16945766
  1. Winton T, Livingston R, Johnson D, et al.：Vinorelbine plus cisplatin vs. observation in resected non-small-cell lung cancer. N Engl J Med. 2005 Jun 23;352(25):2589-97. PMID：15972865
  1. Pignon JP, Tribodet H, Scagliotti GV, et al.：Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group. J Clin Oncol. 2008 Jul 20;26(21):3552-9. PMID：18506026
  1. Kenmotsu H, Yamamoto N, Yamanaka T, et al.: Randomized Phase III Study of Pemetrexed Plus Cisplatin Versus Vinorelbine Plus Cisplatin for Completely Resected Stage II to IIIA Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020 Jul 1;38 (19):2187-2196. PMID：32407216

術後補助化学療法の使い分け

TNM分類第8版を基準に作成。エビデンスの元になった研究で用いられているTNM分類の一部は第7版以前のものであるため、適用にあたっては注意を要する。
 

術後シスプラチン併用療法

CDDP：シスラプチン
VNR：ビノレルビン
PEM：ペメトレキセド
 
＊PEMの投与に際しては下記ビタミンの補充を行う
①葉酸：投与の7日以上前から葉酸として1日1回0.5 mgを連日経口投与する。なお，PEMの投与を中止または終了する場合には，PEM最終投与日から22日目まで可能なかぎり葉酸を投与する。
②ビタミンB12：初回投与の少なくとも7日前に，ビタミンB12として1回1 mgを筋肉内投与する。その後，PEM投与期間中および投与中止後22日目まで9週毎（3サイクル毎）に1回投与する。
 
 

UFT療法

有害事象の発現状況および忍容性をみながら2年を目標に継続する。

術後オシメルチニブ単剤療法

術後アテゾリズマブ療法

有害事象の発現状況および忍容性をみながら1年を目標に継続する。

術前プラチナ製剤併用療法＋免疫チェックポイント阻害薬

＊PEMの投与に際しては下記ビタミンの補充を行う
①葉酸：投与の7日以上前から葉酸として1日1回0.5 mgを連日経口投与する。なお、PEMの投与を中止または終了する場合には、PEM最終投与日から22日目まで可能なかぎり葉酸を投与する。
②ビタミンB12：初回投与の少なくとも7日前に、ビタミンB12として1回1 mgを筋肉内投与する。その後、PEM投与期間中および投与中止後22日目まで9週毎（3サイクル毎）に1回投与する。
 

シスプラチン併用術後化学療法の有用性に関するメタ解析2（サブグループ解析）

病理病期II期、III期でのメリットは明らかであるがIB期に対するメリットは明らかではない。ただし、この研究で用いられているTNM分類はすべて第7版以前のものであるため、適用にあたっては注意を要する。
出典
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1: Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.
著者: Jean-Pierre Pignon, Hélène Tribodet, Giorgio V Scagliotti, Jean-Yves Douillard, Frances A Shepherd, Richard J Stephens, Ariane Dunant, Valter Torri, Rafael Rosell, Lesley Seymour, Stephen G Spiro, Estelle Rolland, Roldano Fossati, Delphine Aubert, Keyue Ding, David Waller, Thierry Le Chevalier, LACE Collaborative Group
雑誌名: J Clin Oncol. 2008 Jul 20;26(21):3552-9. doi: 10.1200/JCO.2007.13.9030. Epub 2008 May 27.
Abstract/Text: PURPOSE: Several recent trials have shown a significant overall survival (OS) benefit from postoperative cisplatin-based chemotherapy in patients with non-small-cell lung cancer (NSCLC). The aim of the Lung Adjuvant Cisplatin Evaluation was to identify treatment options associated with a higher benefit or groups of patients who particularly benefit from postoperative chemotherapy.
PATIENTS AND METHODS: Individual patient data were collected and pooled from the five largest trials (4,584 patients) of cisplatin-based chemotherapy in completely resected patients that were conducted after the 1995 NSCLC meta-analysis. The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analyzed using hazard ratios (HRs) and log-rank tests stratified by trial.
RESULTS: With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82 to 0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy. There was no heterogeneity of chemotherapy effect among trials. The benefit varied with stage (test for trend, P = .04; HR for stage IA = 1.40; 95% CI, 0.95 to 2.06; HR for stage IB = 0.93; 95% CI, 0.78 to 1.10; HR for stage II = 0.83; 95% CI, 0.73 to 0.95; and HR for stage III = 0.83; 95% CI, 0.72 to 0.94). The effect of chemotherapy did not vary significantly (test for interaction, P = .11) with the associated drugs, including vinorelbine (HR = 0.80; 95% CI, 0.70 to 0.91), etoposide or vinca alkaloid (HR = 0.92; 95% CI, 0.80 to 1.07), or other (HR = 0.97; 95% CI, 0.84 to 1.13). Chemotherapy effect was higher in patients with better performance status. There was no interaction between chemotherapy effect and sex, age, histology, type of surgery, planned radiotherapy, or planned total dose of cisplatin.
CONCLUSION: Postoperative cisplatin-based chemotherapy significantly improves survival in patients with NSCLC.
J Clin Oncol. 2008 Jul 20;26(21):3552-9. doi: 10.1200/JCO.2007.13.9030...

シスプラチンベースの術後補助化学療法の有用性に関するメタ解析1（全生存期間）

シスプラチンベースの術後補助化学療法は5年生存率を5.4％改善させる。
（HR 95％CI0.82〜0.96、P＝0.005）
出典
imgimg
1: Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE Collaborative Group.
著者: Jean-Pierre Pignon, Hélène Tribodet, Giorgio V Scagliotti, Jean-Yves Douillard, Frances A Shepherd, Richard J Stephens, Ariane Dunant, Valter Torri, Rafael Rosell, Lesley Seymour, Stephen G Spiro, Estelle Rolland, Roldano Fossati, Delphine Aubert, Keyue Ding, David Waller, Thierry Le Chevalier, LACE Collaborative Group
雑誌名: J Clin Oncol. 2008 Jul 20;26(21):3552-9. doi: 10.1200/JCO.2007.13.9030. Epub 2008 May 27.
Abstract/Text: PURPOSE: Several recent trials have shown a significant overall survival (OS) benefit from postoperative cisplatin-based chemotherapy in patients with non-small-cell lung cancer (NSCLC). The aim of the Lung Adjuvant Cisplatin Evaluation was to identify treatment options associated with a higher benefit or groups of patients who particularly benefit from postoperative chemotherapy.
PATIENTS AND METHODS: Individual patient data were collected and pooled from the five largest trials (4,584 patients) of cisplatin-based chemotherapy in completely resected patients that were conducted after the 1995 NSCLC meta-analysis. The interactions between patient subgroups or treatment types and chemotherapy effect on OS were analyzed using hazard ratios (HRs) and log-rank tests stratified by trial.
RESULTS: With a median follow-up time of 5.2 years, the overall HR of death was 0.89 (95% CI, 0.82 to 0.96; P = .005), corresponding to a 5-year absolute benefit of 5.4% from chemotherapy. There was no heterogeneity of chemotherapy effect among trials. The benefit varied with stage (test for trend, P = .04; HR for stage IA = 1.40; 95% CI, 0.95 to 2.06; HR for stage IB = 0.93; 95% CI, 0.78 to 1.10; HR for stage II = 0.83; 95% CI, 0.73 to 0.95; and HR for stage III = 0.83; 95% CI, 0.72 to 0.94). The effect of chemotherapy did not vary significantly (test for interaction, P = .11) with the associated drugs, including vinorelbine (HR = 0.80; 95% CI, 0.70 to 0.91), etoposide or vinca alkaloid (HR = 0.92; 95% CI, 0.80 to 1.07), or other (HR = 0.97; 95% CI, 0.84 to 1.13). Chemotherapy effect was higher in patients with better performance status. There was no interaction between chemotherapy effect and sex, age, histology, type of surgery, planned radiotherapy, or planned total dose of cisplatin.
CONCLUSION: Postoperative cisplatin-based chemotherapy significantly improves survival in patients with NSCLC.
J Clin Oncol. 2008 Jul 20;26(21):3552-9. doi: 10.1200/JCO.2007.13.9030...