Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy.
Real-world data from a molecular tumor board demonstrates improved outcomes with a precision N-of-One strategy.
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来自分子肿瘤委员会的真实数据表明，精确的 N-of-One 策略可以改善结果。
DOI：
10.1038/s41467-020-18613-3
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发表时间：
2020-10-02
影响因子：
16.6
通讯作者：
Kurzrock R
中科院分区：
文献类型：
--
作者：
Kato S;Kim KH;Lim HJ;Boichard A;Nikanjam M;Weihe E;Kuo DJ;Eskander RN;Goodman A;Galanina N;Fanta PT;Schwab RB;Shatsky R;Plaxe SC;Sharabi A;Stites E;Adashek JJ;Okamura R;Lee S;Lippman SM;Sicklick JK;Kurzrock R
下一代测序(NGS)可以识别新的癌症靶点。然而，解释分子发现和获取药物/临床试验是具有挑战性的。此外，许多肿瘤对单一疗法表现出抗药性。为了实施精确战略，我们发起了一个多学科(基础/翻译/临床研究人员、生物信息学家、遗传学家和来自多个专业的医生)分子肿瘤委员会(MTB)，其中包括一名项目经理，以促进获得临床级生物标记物(血液/组织NGS，包括免疫生物标记物的特异性免疫组织化学/RNA表达，由医生酌情决定)和药物获取专家/临床试验协调员/导航员，以帮助获得药物。MTB全面审查了患者的特征，以开发在治疗医生的指导下、在主方案的主持下实施的N-One治疗。总体而言，265/429名可评估治疗的患者(62%)与≥1推荐药物匹配。86名患者(20%)与MTB推荐的所有药物相匹配，包括联合方案，而38%的患者接受了医生选择的方案，通常方法不匹配/匹配度低。我们的结果显示，接受MTB推荐方案的患者(与医生选择的方案相比)有显著更长的无进展(PFS)和总生存期(OS)，并且与治疗更匹配。高(≥50%)与低(<；50%)匹配分数治疗(大致反映与≥50%与<；50%的改变匹配的治疗)独立地与较长的PFS(风险比[HR]，0.63；95%可信区间[CI]，0.50-0.80；P <； 0.001)和OS(HR，0.67；95%CI，0.50-0.90；P = 0.007)和较高的稳定型疾病≥6个月/部分/完全缓解率(52.1%vs30.4%P <； 0.001)(均为多因素)。总而言之，接受基于MTB的治疗的患者与他们的基因组改变更匹配，匹配程度是包括生存在内的肿瘤学结果改善的独立预测因子。分子肿瘤板(MTB)通常被用作集成临床和分子参数进行临床决策的平台。在这里，作者回顾了在他们机构的MTB上展示的715名癌症患者的结果，并证明接受MTB推荐方案的患者接受了与他们的变化更匹配的治疗，并取得了更好的临床结果。
Next-generation sequencing (NGS) can identify novel cancer targets. However, interpreting the molecular findings and accessing drugs/clinical trials is challenging. Furthermore, many tumors show resistance to monotherapies. To implement a precision strategy, we initiated a multidisciplinary (basic/translational/clinical investigators, bioinformaticians, geneticists, and physicians from multiple specialties) molecular tumor board (MTB), which included a project manager to facilitate obtaining clinical-grade biomarkers (blood/tissue NGS, specific immunohistochemistry/RNA expression including for immune-biomarkers, per physician discretion) and medication-acquisition specialists/clinical trial coordinators/navigators to assist with medication access. The MTB comprehensively reviewed patient characteristics to develop N-of-One treatments implemented by the treating physician’s direction under the auspices of a master protocol. Overall, 265/429 therapy-evaluable patients (62%) were matched to ≥1 recommended drug. Eighty-six patients (20%) matched to all drugs recommended by MTB, including combinatorial approaches, while 38% received physician’s choice regimen, generally with unmatched approach/low degree of matching. Our results show that patients who receive MTB-recommended regimens (versus physician choice) have significantly longer progression-free (PFS) and overall survival (OS), and are better matched to therapy. High (≥50%) versus low (<50%) Matching Score therapy (roughly reflecting therapy matched to ≥50% versus <50% of alterations) independently correlates with longer PFS (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.50–0.80; P < 0.001) and OS (HR, 0.67; 95% CI, 0.50–0.90; P = 0.007) and higher stable disease ≥6 months/partial/complete remission rate (52.1% versus 30.4% P < 0.001) (all multivariate). In conclusion, patients who receive MTB-based therapy are better matched to their genomic alterations, and the degree of matching is an independent predictor of improved oncologic outcomes including survival. A molecular tumor board (MTB) is often used as a platform that integrates clinical and molecular parameters for clinical decision making. Here, the authors review the outcome of 715 cancer patients presented at their institution’s MTB, and demonstrate that patients who received a MTB-recommended regimen received therapy that was better matched to their alterations and achieved better clinical outcomes.
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影响因子：
11.2
作者：
Kato S;Krishnamurthy N;Banks KC;De P;Williams K;Williams C;Leyland-Jones B;Lippman SM;Lanman RB;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
28.2
作者：
Drilon A;Siena S;Ou SI;Patel M;Ahn MJ;Lee J;Bauer TM;Farago AF;Wheler JJ;Liu SV;Doebele R;Giannetta L;Cerea G;Marrapese G;Schirru M;Amatu A;Bencardino K;Palmeri L;Sartore-Bianchi A;Vanzulli A;Cresta S;Damian S;Duca M;Ardini E;Li G;Christiansen J;Kowalski K;Johnson AD;Patel R;Luo D;Chow-Maneval E;Hornby Z;Multani PS;Shaw AT;De Braud FG
通讯作者：
De Braud FG
DOI：
10.1056/nejmoa1714448
发表时间：
2018-02-22
期刊：
The New England journal of medicine
影响因子：
--
作者：
Drilon A;Laetsch TW;Kummar S;DuBois SG;Lassen UN;Demetri GD;Nathenson M;Doebele RC;Farago AF;Pappo AS;Turpin B;Dowlati A;Brose MS;Mascarenhas L;Federman N;Berlin J;El-Deiry WS;Baik C;Deeken J;Boni V;Nagasubramanian R;Taylor M;Rudzinski ER;Meric-Bernstam F;Sohal DPS;Ma PC;Raez LE;Hechtman JF;Benayed R;Ladanyi M;Tuch BB;Ebata K;Cruickshank S;Ku NC;Cox MC;Hawkins DS;Hong DS;Hyman DM
通讯作者：
Hyman DM
影响因子：
4.3
作者：
Kurzrock, Razelle;Giles, Francis J.
通讯作者：
Giles, Francis J.
影响因子：
2.1
作者：
Pishvaian, Michael J.;Blais, Edik M.;Madhavan, Subha
通讯作者：
Madhavan, Subha