Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-628
Kalo Roland Millogo, Delphine Kabore, S. Traoré
Acute leukaemias constitute 9.04% of malignant hemopathies (Burkina Faso, 2015). Their manifestations are mainly haematological, however other less frequent attacks are possible. We report here for the first time in Burkina Faso, three cases of ocular localizations in young adults. Observation 1: S.I, male, 17-year-old patient, student living in Ouagadougou with a history of recurrent sore throat and ear infections. He was admitted for asthenia and pallor in the context of polytransfusion. The myelogram showed a rich marrow marked by the presence of 15% blast cells. Ophthalmologic examination reported visual acuity of 1/10, stage II proptosis and lower chemosis, and massive retinal and macular hemorrhage. Chemotherapy could not be performed. he died a week later. Observation 2: TB, male, 23-year-old patient, welder, suffering from acute lymphoblastic leukemia diagnosed in front of a severe recurrent anemia and confirmed by a myelogram, showing a rich marrow infiltrated by lymphoblasts representing 47% of the medullary cells. The ophthalmologic examination revealed conjunctival-palpebral infiltration by acute leukemia with myogenic ptosis. The evolution was marked by an improvement in symptoms after a cure according to the Vincristine-Prednisone protocol and he was discharged from hospital weeks later. He was subsequently lost to follow-up. Observation 3: KK male, 25-year-old patient, artisanal miner residing in Ouagadougou with a history of peptic ulcer disease, carrier of acute myeloid leukemia (AML) confirmed by a myelogram. The ophthalmologic examination concludes with a bilateral inflammatory orthopathy with an exposure keratitis on site of AML. He received transfusion of concentrates of red blood cells and platelets, as well as corticosteroid therapy for 04 days. The following was marked by a rapid worsening of the symptoms and the death of the patient a week later. Conclusion: The extra-haematological manifestations of acute leukemia are rare. They are associated with a pejorative prognosis. This series of 03 cases that we report is the first described to date in our context. Citation Format: Kalo Roland Millogo, Delphine Kabore, Solo Traore. Ophtalmological manifestations of acute leukemias at university hospital center Yalgado Ouedrago [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 628.
急性白血病占恶性血液病的9.04%(布基纳法索，2015年)。其主要表现为血液病，但也可能有其他不太常见的发作。我们在这里报告首次在布基纳法索，三例眼部定位的年轻人。观察1:S.I，男，17岁，学生，居住在瓦加杜古，有复发性喉咙痛和耳部感染史。在多次输血的情况下，他因虚弱和苍白而入院。骨髓造影显示骨髓丰富，有15%的原始细胞。眼科检查报告视力为1/10,II期突出和下部化脓，大量视网膜和黄斑出血。化疗不能进行。一周后，他去世了。观察2:结核，男，23岁，焊工，患有急性淋巴细胞白血病，在严重复发性贫血前诊断，骨髓造影证实，骨髓丰富，淋巴细胞浸润，占髓细胞的47%。眼科检查发现结膜-眼睑浸润急性白血病伴肌源性上睑下垂。根据长春新碱-强的松治疗方案治疗后症状有所改善，几周后出院。他后来失去了随访。观察3:KK男，25岁，瓦加杜古手工矿工，消化性溃疡病史，骨髓造影证实急性髓性白血病(AML)携带者。眼科检查发现双侧炎性矫形伴急性髓性白血病部位暴露性角膜炎。他接受了红细胞和血小板浓缩液的输注，并接受了皮质类固醇治疗，持续了04天。接下来的特点是症状迅速恶化，一周后病人死亡。结论:急性白血病血液学外表现少见。它们与不良预后有关。我们报告的这一系列03例病例是迄今为止在我们的上下文中首次描述的。引文格式:Kalo Roland Millogo, Delphine Kabore, Solo Traore。Yalgado Ouedrago大学医院中心急性白血病的眼科表现。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):628。
{"title":"Abstract 628: Ophtalmological manifestations of acute leukemias at university hospital center Yalgado Ouedrago","authors":"Kalo Roland Millogo, Delphine Kabore, S. Traoré","doi":"10.1158/1538-7445.AM2021-628","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-628","url":null,"abstract":"Acute leukaemias constitute 9.04% of malignant hemopathies (Burkina Faso, 2015). Their manifestations are mainly haematological, however other less frequent attacks are possible. We report here for the first time in Burkina Faso, three cases of ocular localizations in young adults. Observation 1: S.I, male, 17-year-old patient, student living in Ouagadougou with a history of recurrent sore throat and ear infections. He was admitted for asthenia and pallor in the context of polytransfusion. The myelogram showed a rich marrow marked by the presence of 15% blast cells. Ophthalmologic examination reported visual acuity of 1/10, stage II proptosis and lower chemosis, and massive retinal and macular hemorrhage. Chemotherapy could not be performed. he died a week later. Observation 2: TB, male, 23-year-old patient, welder, suffering from acute lymphoblastic leukemia diagnosed in front of a severe recurrent anemia and confirmed by a myelogram, showing a rich marrow infiltrated by lymphoblasts representing 47% of the medullary cells. The ophthalmologic examination revealed conjunctival-palpebral infiltration by acute leukemia with myogenic ptosis. The evolution was marked by an improvement in symptoms after a cure according to the Vincristine-Prednisone protocol and he was discharged from hospital weeks later. He was subsequently lost to follow-up. Observation 3: KK male, 25-year-old patient, artisanal miner residing in Ouagadougou with a history of peptic ulcer disease, carrier of acute myeloid leukemia (AML) confirmed by a myelogram. The ophthalmologic examination concludes with a bilateral inflammatory orthopathy with an exposure keratitis on site of AML. He received transfusion of concentrates of red blood cells and platelets, as well as corticosteroid therapy for 04 days. The following was marked by a rapid worsening of the symptoms and the death of the patient a week later. Conclusion: The extra-haematological manifestations of acute leukemia are rare. They are associated with a pejorative prognosis. This series of 03 cases that we report is the first described to date in our context. Citation Format: Kalo Roland Millogo, Delphine Kabore, Solo Traore. Ophtalmological manifestations of acute leukemias at university hospital center Yalgado Ouedrago [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 628.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89865508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-683
Devon C. Barry, Natalie A Hartung, C. Williams
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Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-674
A. Chauhan, C. Kunos, R. Khouli, J. Kolesar, Heidi L. Weiss, Bill Carson, M. Kidd, J. Beumer, S. Arnold, E. Kohn, L. Anthony
{"title":"Abstract 674: A phase I trial of Triapine and Lutetium Lu 177 Dotatate in combination for well-differentiated somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (GEP-NETs)","authors":"A. Chauhan, C. Kunos, R. Khouli, J. Kolesar, Heidi L. Weiss, Bill Carson, M. Kidd, J. Beumer, S. Arnold, E. Kohn, L. Anthony","doi":"10.1158/1538-7445.AM2021-674","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-674","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"46 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73481049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-567
Shuo Li, W. Zeng, X. Ni, M. Stackpole, Yonggang Zhou, Z. Noor, Zuyang Yuan, E. Garon, S. Dubinett, Wenyuan Li, X. Zhou
Monitoring cancer patients for the early detection of minimal residual disease (MRD), cancer recurrence, and cancer progression is essential for assessing treatment response and predicting early relapse during/after treatment. Plasma cell-free DNA (cfDNA) provides unique opportunities for cancer monitoring given its non-invasive and comprehensive sampling of heterogeneous tumor clones. However, the low tumor content in cfDNA poses a major challenge for detecting tumor signals. Previous methods mostly rely on deep sequencing of small panels to capture the tumor signal. These methods usually require the labor-intensive design of customized gene panel, yet fail to identify the evolving tumor, which is essential for detecting second primary diseases or emerging subclones. To address these limitations, here we present OncoMonitor, a cancer monitoring method that comprehensively analyzes tumor mutations in cfDNA whole-exome sequencing data. Taking advantage of the availability of mutation information across the whole exome, our method (1) integrates all clonal tumor mutations identified from pre-treatment cfDNA samples (or tumor samples) to compensate for low tumor fraction in cfDNA, (2) suppresses sequencing errors at read level with an accurate random forest classifier to model the observed features from cfDNA fragments and further enhance the tumor signal, (3) builds sample-specific background noise distributions to predict recurrence and MRD to avoid interference from inter-individual variations and inter-experimental biases, and (4) detects tumor changes, especially second primary diseases, by identifying newly emerging tumor mutations de novo. Combining these techniques, for the first time, we show that OncoMonitor can sensitively and specifically detect both cancer recurrence/MRD and secondary primary cancers from plasma samples with low tumor fraction. Using simulated cfDNA sequence data with artificial mutation spike-ins, our method can detect recurrence at 0.025% tumor fraction with > 95% sensitivity and 95% specificity, and the second primary disease at 0.1% tumor fraction with around 75% sensitivity and 100% specificity. In a cohort of 9 non-small-cell lung cancer patients, we show that OncoMonitor can provide comprehensive tumor changes for treatment response prediction and capture emerging tumor clones; this cannot be achieved by previous methods that are based only on mutations in the pre-treatment surgery samples. In summary, with broad genomic sequencing coverage and comprehensive mutation analysis, our method can identify patients suffering from MRD or cancer recurrence/progression, provide a thorough view of their tumor status, and enable early intervention and personalized treatment. Citation Format: Shuo Li, Weihua Zeng, Xiaohui Ni, Mary L. Stackpole, Yonggang Zhou, Zorawar Noor, Zuyang Yuan, Edward B. Garon, Steven M. Dubinett, Wenyuan Li, Xianghong Zhou. cMonitor: Comprehensive and sensitive monitoring of diverse cancer treatment
监测癌症患者的早期发现微小残留疾病(MRD)、癌症复发和癌症进展对于评估治疗反应和预测治疗期间/之后的早期复发至关重要。无浆细胞DNA (cfDNA)为癌症监测提供了独特的机会，因为它对异质性肿瘤克隆进行了非侵入性和全面的采样。然而，cfDNA的低肿瘤含量给检测肿瘤信号带来了重大挑战。以前的方法大多依赖于小面板的深度测序来捕获肿瘤信号。这些方法通常需要耗费大量人力设计定制的基因面板，但无法识别正在进化的肿瘤，而这对于检测第二原发疾病或新出现的亚克隆至关重要。为了解决这些限制，我们提出了OncoMonitor，一种全面分析cfDNA全外显子组测序数据中肿瘤突变的癌症监测方法。利用整个外显子组突变信息的可用性，我们的方法(1)整合了从预处理cfDNA样本(或肿瘤样本)中鉴定出的所有克隆肿瘤突变，以弥补cfDNA中较低的肿瘤比例;(2)使用精确的随机森林分类器在读取水平上抑制测序错误，以模拟cfDNA片段中观察到的特征，进一步增强肿瘤信号。(3)建立样本特异性背景噪声分布来预测复发和MRD，以避免个体间差异和实验间偏差的干扰;(4)通过识别新出现的肿瘤突变来检测肿瘤的变化，特别是第二原发疾病。结合这些技术，我们首次证明OncoMonitor可以从低肿瘤比例的血浆样本中敏感和特异性地检测癌症复发/MRD和继发性原发性癌症。使用模拟的cfDNA序列数据和人工突变尖峰，我们的方法可以在0.025%的肿瘤部分检测复发，灵敏度> 95%，特异性95%;在0.1%的肿瘤部分检测第二原发疾病，灵敏度约75%，特异性100%。在9例非小细胞肺癌患者的队列研究中，我们发现OncoMonitor可以提供全面的肿瘤变化，用于预测治疗反应并捕获新出现的肿瘤克隆;这不能通过以前的方法来实现，这些方法仅基于治疗前手术样本中的突变。总之，通过广泛的基因组测序覆盖和全面的突变分析，我们的方法可以识别患有MRD或癌症复发/进展的患者，提供对其肿瘤状态的全面了解，并使早期干预和个性化治疗成为可能。引用格式:李硕，曾卫华，倪晓辉，Mary L. Stackpole，周永刚，Zorawar Noor，袁祖阳，Edward B. Garon, Steven M. Dubinett，李文渊，周祥红。cMonitor:通过血浆cfDNA外显子组全突变分析，全面、灵敏地监测多种癌症治疗结果[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):567。
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Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-638
Liya Xu, Mary E. Kim, Ashley Polski, Rishvanth K. Prabakar, Chen-Ching Peng, P. Chévez-Barrios, Jonathan W. Kim, R. Shah, R. Jubran, P. Kuhn, D. Cobrinik, J. Hicks, J. Berry
Purpose: All previous studies of retinoblastoma (RB) aqueous humor (AH) analysis for tumor-derived cell-free DNA (cfDNA) have focused on sampling AH from eyes undergoing therapy; results from AH liquid biopsy at the time of diagnosis have not yet been published. Herein, we detail the diagnostic and prognostic genomic biomarkers found in the AH cfDNA from 7 RB eyes at diagnosis, each with longitudinal evaluation of over 12 months in follow-up. Methods: Subjects included 7 eyes of 6 RB patients who underwent AH sampling at diagnosis. CfDNA from each AH sample was isolated and sequenced to assess genome-wide somatic copy number alterations (SCNAs), followed by targeted resequencing and mutation detection using a custom hybridization panel for RB1 and MYCN. Results were compared to peripheral blood RB1 testing and matched tumor samples, when available. Tumor fraction (TFx) was calculated using ichorCNA. Results: Five of 7 diagnostic AH samples contained highly recurrent RB SCNAs, 4 with large scale alterations and 1 with a focal RB1 gene deletion. Mutational analysis of AH cfDNA identified pathogenic somatic variants in 5 diagnostic AH samples with high variant allele frequency, while the remaining 2 diagnostic AH samples had either a high TFx from SCNAs or a focal MYCN amplification. Taken together, somatic tumoral genomic information was detected in all 7 diagnostic AH samples. The 2 eyes that required enucleation had poor prognostic biomarkers (chromosome 6p gain and MYCN amplification) present at the time of diagnosis. TFx from longitudinal AH sampling corresponded to treatment response over time in all cases for which sequential AH samples were available. Conclusions: This study demonstrates that AH sampling at diagnosis is both feasible and safe. Molecular profiling of AH provides a plethora of diagnostic and prognostic information from only a single 0.1 mL AH sample. 1 Citation Format: Liya Xu, Mary E. Kim, Ashley Polski, Rishvanth K. Prabakar, Chen-Ching Peng, Patricia Chevez-Barrios, Jonathan W. Kim, Rachana Shah, Rima Jubran, Peter Kuhn, David Cobrinik, James Hicks, Jesse L. Berry. Enhancing the molecular diagnosis, prognosis, and treatment monitoring of retinoblastoma using cell free DNA in aqueous humor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 638.
目的:以前所有关于视网膜母细胞瘤(RB)房水(AH)分析肿瘤来源的无细胞DNA (cfDNA)的研究都集中在从接受治疗的眼睛中取样AH;AH液体活检在诊断时的结果尚未发表。在此，我们详细介绍了在诊断时7只RB眼睛的AH cfDNA中发现的诊断和预后基因组生物标志物，每只眼睛都进行了超过12个月的纵向随访评估。方法:研究对象包括6例RB患者的7只眼，在诊断时进行AH取样。从每个AH样本中分离CfDNA并测序以评估全基因组体细胞拷贝数改变(SCNAs)，然后使用定制的RB1和MYCN杂交面板进行靶向重测序和突变检测。将结果与外周血RB1检测和匹配的肿瘤样本(如果有)进行比较。使用ichorCNA计算肿瘤分数(TFx)。结果:7个AH诊断样本中有5个含有高复发性RB SCNAs, 4个具有大规模改变，1个具有局灶性RB1基因缺失。AH cfDNA突变分析在5个AH诊断样本中发现了高变异等位基因频率的致病性体细胞变异，而其余2个AH诊断样本要么具有来自SCNAs的高TFx，要么具有局灶性MYCN扩增。综上所述，在所有7个AH诊断样本中检测到体细胞肿瘤基因组信息。2只需要去核的眼睛在诊断时存在预后不良的生物标志物(染色体6p增加和MYCN扩增)。在所有可获得连续AH样本的病例中，纵向AH采样的TFx与随时间推移的治疗反应相对应。结论:本研究证明在诊断时AH取样是可行和安全的。AH的分子谱分析提供了大量的诊断和预后信息，仅从一个单一的0.1 mL AH样品。1引文格式:Liya Xu, Mary E. Kim, Ashley Polski, Rishvanth K. Prabakar, Chen-Ching Peng, Patricia Chevez-Barrios, Jonathan W. Kim, Rachana Shah, Rima Jubran, Peter Kuhn, David Cobrinik, James Hicks, Jesse L. Berry。利用房水游离DNA增强视网膜母细胞瘤的分子诊断、预后和治疗监测[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):638。
{"title":"Abstract 638: Enhancing the molecular diagnosis, prognosis, and treatment monitoring of retinoblastoma using cell free DNA in aqueous humor","authors":"Liya Xu, Mary E. Kim, Ashley Polski, Rishvanth K. Prabakar, Chen-Ching Peng, P. Chévez-Barrios, Jonathan W. Kim, R. Shah, R. Jubran, P. Kuhn, D. Cobrinik, J. Hicks, J. Berry","doi":"10.1158/1538-7445.AM2021-638","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-638","url":null,"abstract":"Purpose: All previous studies of retinoblastoma (RB) aqueous humor (AH) analysis for tumor-derived cell-free DNA (cfDNA) have focused on sampling AH from eyes undergoing therapy; results from AH liquid biopsy at the time of diagnosis have not yet been published. Herein, we detail the diagnostic and prognostic genomic biomarkers found in the AH cfDNA from 7 RB eyes at diagnosis, each with longitudinal evaluation of over 12 months in follow-up. Methods: Subjects included 7 eyes of 6 RB patients who underwent AH sampling at diagnosis. CfDNA from each AH sample was isolated and sequenced to assess genome-wide somatic copy number alterations (SCNAs), followed by targeted resequencing and mutation detection using a custom hybridization panel for RB1 and MYCN. Results were compared to peripheral blood RB1 testing and matched tumor samples, when available. Tumor fraction (TFx) was calculated using ichorCNA. Results: Five of 7 diagnostic AH samples contained highly recurrent RB SCNAs, 4 with large scale alterations and 1 with a focal RB1 gene deletion. Mutational analysis of AH cfDNA identified pathogenic somatic variants in 5 diagnostic AH samples with high variant allele frequency, while the remaining 2 diagnostic AH samples had either a high TFx from SCNAs or a focal MYCN amplification. Taken together, somatic tumoral genomic information was detected in all 7 diagnostic AH samples. The 2 eyes that required enucleation had poor prognostic biomarkers (chromosome 6p gain and MYCN amplification) present at the time of diagnosis. TFx from longitudinal AH sampling corresponded to treatment response over time in all cases for which sequential AH samples were available. Conclusions: This study demonstrates that AH sampling at diagnosis is both feasible and safe. Molecular profiling of AH provides a plethora of diagnostic and prognostic information from only a single 0.1 mL AH sample. 1 Citation Format: Liya Xu, Mary E. Kim, Ashley Polski, Rishvanth K. Prabakar, Chen-Ching Peng, Patricia Chevez-Barrios, Jonathan W. Kim, Rachana Shah, Rima Jubran, Peter Kuhn, David Cobrinik, James Hicks, Jesse L. Berry. Enhancing the molecular diagnosis, prognosis, and treatment monitoring of retinoblastoma using cell free DNA in aqueous humor [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 638.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"175 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75493387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-457
S. Figueroa, Joseph Vargas, Jason A. Ramos
Introduction In the 2016 World Health Organization Central Nervous System Tumor Classification, diffuse gliomas were reclassified to include astrocytic tumors (grade II and III), oligodendrogliomas (grade II and III), and grade IV glioblastomas with diffuse astrocytoma being distinct from the diffuse gliomas. This reclassification is due to the abundance of IDH1 mutations in many of these tumors. A much better outcome has been observed in these patients than those without this mutation. IDH1 mutation of the R132H type constitutes more than 90% of all IDH1 and IDH2 mutations. Further, IDH1 IHC is now widely applied for the differential diagnosis of these tumors. There are two distinct IDH1 R132H clones on the market, the H09 and IHC132. Comparing these markers for the IDH1 R132H mutations by IHC can help determine if one is superior for diagnostics. Materials and Methods IHC was performed on 3-5 um thick formalin-fixed, paraffin-embedded (FFPE) brain tissue arrays containing glioblastoma, astrocytoma, oligoastrocytoma, oligodendroglioma with adjacent normal tissue (US Biomax, Derwood, USA). These slides were deparaffinized, and peroxidase blocked in the usual manner. Slides were then subjected to HIER in a pressure cooker using a citrate-based buffer at 110°C for 15 minutes before being stained on a semi-automated instrument. The slides were stained with rabbit monoclonal IDH1 R132H antibody H09 (Dianova, Hamburg, Germany) and mouse monoclonal IDH1 R132H antibody IHC132 (GenomeMe, Richmond, Canada) at concentrations and protocols predetermined to match staining intensity. Results The mouse monoclonal anti-IDH1 R132H IHC132 has shown that it is analogous to the current IDH1 R132H [H09]. Upon review of the data, IHC132 marker stains a higher percentage of cases in glioblastoma compared to H09 (11%, n=36) and equal in astrocytoma (73%, n=15), oligoastrocytoma (75%, n=4), oligodendroglioma (100%, n=8). Neither clone stained normal brain tissue per negative controls. Conclusion Mouse monoclonal anti-IDH1 R132H [IHC132] compared with that of the rabbit monoclonal anti-IDH1 R132H [H09] showed equal sensitivity for astrocytoma, oligodendroglioma, and oligoastrocytomas with higher sensitivity for glioblastoma. The results provide evidence to support a higher percentage of positive staining and equal or greater intensity for clone IHC132 versus H09. Citation Format: Sara Figueroa, Joseph Vargas, Jason Ramos. A comparison of IDH1 R132H [H09] and [IHC132] antibodies on diffuse gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 457.
{"title":"Abstract 457: A comparison of IDH1 R132H [H09] and [IHC132] antibodies on diffuse gliomas","authors":"S. Figueroa, Joseph Vargas, Jason A. Ramos","doi":"10.1158/1538-7445.AM2021-457","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-457","url":null,"abstract":"Introduction In the 2016 World Health Organization Central Nervous System Tumor Classification, diffuse gliomas were reclassified to include astrocytic tumors (grade II and III), oligodendrogliomas (grade II and III), and grade IV glioblastomas with diffuse astrocytoma being distinct from the diffuse gliomas. This reclassification is due to the abundance of IDH1 mutations in many of these tumors. A much better outcome has been observed in these patients than those without this mutation. IDH1 mutation of the R132H type constitutes more than 90% of all IDH1 and IDH2 mutations. Further, IDH1 IHC is now widely applied for the differential diagnosis of these tumors. There are two distinct IDH1 R132H clones on the market, the H09 and IHC132. Comparing these markers for the IDH1 R132H mutations by IHC can help determine if one is superior for diagnostics. Materials and Methods IHC was performed on 3-5 um thick formalin-fixed, paraffin-embedded (FFPE) brain tissue arrays containing glioblastoma, astrocytoma, oligoastrocytoma, oligodendroglioma with adjacent normal tissue (US Biomax, Derwood, USA). These slides were deparaffinized, and peroxidase blocked in the usual manner. Slides were then subjected to HIER in a pressure cooker using a citrate-based buffer at 110°C for 15 minutes before being stained on a semi-automated instrument. The slides were stained with rabbit monoclonal IDH1 R132H antibody H09 (Dianova, Hamburg, Germany) and mouse monoclonal IDH1 R132H antibody IHC132 (GenomeMe, Richmond, Canada) at concentrations and protocols predetermined to match staining intensity. Results The mouse monoclonal anti-IDH1 R132H IHC132 has shown that it is analogous to the current IDH1 R132H [H09]. Upon review of the data, IHC132 marker stains a higher percentage of cases in glioblastoma compared to H09 (11%, n=36) and equal in astrocytoma (73%, n=15), oligoastrocytoma (75%, n=4), oligodendroglioma (100%, n=8). Neither clone stained normal brain tissue per negative controls. Conclusion Mouse monoclonal anti-IDH1 R132H [IHC132] compared with that of the rabbit monoclonal anti-IDH1 R132H [H09] showed equal sensitivity for astrocytoma, oligodendroglioma, and oligoastrocytomas with higher sensitivity for glioblastoma. The results provide evidence to support a higher percentage of positive staining and equal or greater intensity for clone IHC132 versus H09. Citation Format: Sara Figueroa, Joseph Vargas, Jason Ramos. A comparison of IDH1 R132H [H09] and [IHC132] antibodies on diffuse gliomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 457.","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75552855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-614
F. D. Jong, T. Laajala, R. Hoedemaeker, S. Rinaldetti, Jolien T. M. Mensink, A. V. D. Made, D. Schoot, E. Boevé, E. Zwarthoff, J. Boormans, D. Theodorescu, J. Costello, T. Zuiverloon
{"title":"Abstract 614: Transcriptomic analysis of BCG-treated T1HG bladder cancer patients identifies an EMT-basal subgroup with immune suppressive characteristics at high risk of BCG-failure","authors":"F. D. Jong, T. Laajala, R. Hoedemaeker, S. Rinaldetti, Jolien T. M. Mensink, A. V. D. Made, D. Schoot, E. Boevé, E. Zwarthoff, J. Boormans, D. Theodorescu, J. Costello, T. Zuiverloon","doi":"10.1158/1538-7445.AM2021-614","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-614","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77884031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-552
J. Chapman, W. Pierson, K. Smith-McCune, Geovanni Pineda, R. Vattakalam, A. Ross, M. Mills, Carlos J. Suarez, T. Davis, R. Edwards, M. Boisen, J. Ford, J. Hou, Hsin-Ta Wu, S. Dashner, E. Kalashnikova, Angel Rodriguez, B. Zimmermann, S. Sawyer, H. Sethi, A. Aleshin
Introduction: Epithelial ovarian, fallopian tube, and peritoneal cancer (EOC) is the most lethal gynecologic malignancy with a 5-year survival rate of 47%. While primary treatment generally results in remission, most patients relapse within 3 years. CA-125 is a commonly used biomarker for recurrence detection, however, it lacks specificity and is not associated with improved survival. Here we examine the utility of circulating tumor DNA (ctDNA) as a biomarker for EOC by assessing its relationship to patient outcome and CA-125 when measured pre-surgically and during patient monitoring. Methods: This study included patients diagnosed with stage I-IV EOC with plasma samples collected pre-surgically (n=44) and a group of patients (n=22) with serially collected samples after surgery. Median follow-up for patients with pre-surgical samples and with prospectively collected samples was 29 months (range: 6-150) and 15 months (range: 0.6-26), respectively. Whole exome sequencing was performed on patient tumors and matched normal tissue to design patient-specific ctDNA assays (bespoke mPCR NGS assay) for variant detection in plasma samples. The relationship between ctDNA status, CA-125 levels, and recurrence-free survival (RFS) were evaluated (Fisher9s exact, log-rank test). Results: Among patients with presurgical plasma samples high-grade serous was the most common histological subtype 66% (29/44). Endometrioid represented 11% (5/44) of tumors and 23% (10/44) were tumors of other epithelial subtypes. In this cohort 75% (33/44) had early-stage disease, 7% (3/44) were metastatic and 18% (8/44) had the unstaged disease. The presence of ctDNA was observed in 73% of samples at baseline with detection rates of 69% (20/29) for serous and 80% (4/5) for endometrioid histologies. Pre-surgical ctDNA detection was significantly associated with a higher grade (p=0.003). All patients with ctDNA negative status at baseline (n=12) survived until the end of follow-up (median: 25 months), while 3 deaths were observed among ctDNA positive patients (n=32; p=0.003). In the sub-cohort of patients with prospective post-surgical plasma collection, ctDNA was observed in samples of all patients who relapsed (7/7; 100% sensitivity). ctDNA detection preceded radiological findings by a median of 9 months (range: 2-36). None of the patients with ctDNA negative status within 6 months after enrollment experienced disease progression (13/13; 100% specificity). The presence of ctDNA was observed to be a strong predictor of relapse (HR: 12.75, 95%CI: 1.7-94 p Conclusions: The presence of ctDNA post-surgically is highly prognostic of decreased RFS and was found to be a stronger predictor of disease progression than CA-125 monitoring. These results suggest that monitoring ctDNA could be a useful tool in clinical decision making for patients with EOC. Citation Format: Jocelyn S. Chapman, William E. Pierson, Karen Smith-McCune, Geovanni Pineda, Reena M. Vattakalam, Alexandra Ross, Meredith A.
上皮性卵巢、输卵管和腹膜癌(EOC)是最致命的妇科恶性肿瘤，5年生存率为47%。虽然初步治疗通常会导致缓解，但大多数患者在3年内复发。CA-125是一种常用的复发检测生物标志物，然而，它缺乏特异性，与生存率的提高无关。在这里，我们研究循环肿瘤DNA (ctDNA)作为EOC的生物标志物的效用，通过评估其与患者预后和CA-125的关系，在术前和患者监测期间进行测量。方法:本研究纳入术前收集血浆样本的I-IV期EOC患者(n=44)和术后连续收集血浆样本的患者(n=22)。术前样本和前瞻性样本的中位随访时间分别为29个月(范围:6-150)和15个月(范围:0.6-26)。对患者肿瘤和匹配的正常组织进行全外显子组测序，设计患者特异性ctDNA测定(定制的mPCR NGS测定)，用于血浆样本中的变异检测。评估ctDNA状态、CA-125水平和无复发生存(RFS)之间的关系(fisher 9的精确对数秩检验)。结果:术前血浆标本中，高级别浆液是最常见的组织学亚型，占66%(29/44)。子宫内膜样肿瘤占11%(5/44)，其他上皮亚型肿瘤占23%(10/44)。在该队列中，75%(33/44)为早期疾病，7%(3/44)为转移性疾病，18%(8/44)为未分期疾病。基线时，73%的样本中观察到ctDNA的存在，浆液组织的检测率为69%(20/29)，子宫内膜样组织的检测率为80%(4/5)。术前ctDNA检测与较高的分级显著相关(p=0.003)。基线时ctDNA阴性的所有患者(n=12)存活至随访结束(中位:25个月)，而ctDNA阳性的患者中有3例死亡(n=32;p = 0.003)。在前瞻性术后血浆采集患者的亚队列中，在所有复发患者的样本中观察到ctDNA (7/7;100%的敏感性)。ctDNA检测比放射学发现早中位9个月(范围:2-36)。入组后6个月内，ctDNA阴性的患者均未出现疾病进展(13/13;特异性100%)。ctDNA的存在被观察到是复发的一个强有力的预测因子(HR: 12.75, 95%CI: 1.7-94 p)。结论:术后ctDNA的存在是RFS下降的高度预后因素，并且被发现是比CA-125监测更强的疾病进展预测因子。这些结果表明，监测ctDNA可能是EOC患者临床决策的有用工具。引文格式:Jocelyn S. Chapman, William E. Pierson, Karen Smith-McCune, Geovanni Pineda, Reena M. Vattakalam, Alexandra Ross, Meredith A. Mills, Carlos J. Suarez, Tracy Davis, Robert P. Edwards, Michelle Boisen, James M. Ford, June Y. Hou, hsinta Wu, Scott Dashner, Ekaterina Kalashnikova, Angel Rodriguez, Bernhard Zimmermann, Sarah Sawyer, Himanshu Sethi, Alexey Aleshin。循环肿瘤DNA预测卵巢癌患者疾病复发[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):552。
{"title":"Abstract 552: Circulating tumor DNA predicts disease recurrence in ovarian cancer patients","authors":"J. Chapman, W. Pierson, K. Smith-McCune, Geovanni Pineda, R. Vattakalam, A. Ross, M. Mills, Carlos J. Suarez, T. Davis, R. Edwards, M. Boisen, J. Ford, J. Hou, Hsin-Ta Wu, S. Dashner, E. Kalashnikova, Angel Rodriguez, B. Zimmermann, S. Sawyer, H. Sethi, A. Aleshin","doi":"10.1158/1538-7445.AM2021-552","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-552","url":null,"abstract":"Introduction: Epithelial ovarian, fallopian tube, and peritoneal cancer (EOC) is the most lethal gynecologic malignancy with a 5-year survival rate of 47%. While primary treatment generally results in remission, most patients relapse within 3 years. CA-125 is a commonly used biomarker for recurrence detection, however, it lacks specificity and is not associated with improved survival. Here we examine the utility of circulating tumor DNA (ctDNA) as a biomarker for EOC by assessing its relationship to patient outcome and CA-125 when measured pre-surgically and during patient monitoring. Methods: This study included patients diagnosed with stage I-IV EOC with plasma samples collected pre-surgically (n=44) and a group of patients (n=22) with serially collected samples after surgery. Median follow-up for patients with pre-surgical samples and with prospectively collected samples was 29 months (range: 6-150) and 15 months (range: 0.6-26), respectively. Whole exome sequencing was performed on patient tumors and matched normal tissue to design patient-specific ctDNA assays (bespoke mPCR NGS assay) for variant detection in plasma samples. The relationship between ctDNA status, CA-125 levels, and recurrence-free survival (RFS) were evaluated (Fisher9s exact, log-rank test). Results: Among patients with presurgical plasma samples high-grade serous was the most common histological subtype 66% (29/44). Endometrioid represented 11% (5/44) of tumors and 23% (10/44) were tumors of other epithelial subtypes. In this cohort 75% (33/44) had early-stage disease, 7% (3/44) were metastatic and 18% (8/44) had the unstaged disease. The presence of ctDNA was observed in 73% of samples at baseline with detection rates of 69% (20/29) for serous and 80% (4/5) for endometrioid histologies. Pre-surgical ctDNA detection was significantly associated with a higher grade (p=0.003). All patients with ctDNA negative status at baseline (n=12) survived until the end of follow-up (median: 25 months), while 3 deaths were observed among ctDNA positive patients (n=32; p=0.003). In the sub-cohort of patients with prospective post-surgical plasma collection, ctDNA was observed in samples of all patients who relapsed (7/7; 100% sensitivity). ctDNA detection preceded radiological findings by a median of 9 months (range: 2-36). None of the patients with ctDNA negative status within 6 months after enrollment experienced disease progression (13/13; 100% specificity). The presence of ctDNA was observed to be a strong predictor of relapse (HR: 12.75, 95%CI: 1.7-94 p Conclusions: The presence of ctDNA post-surgically is highly prognostic of decreased RFS and was found to be a stronger predictor of disease progression than CA-125 monitoring. These results suggest that monitoring ctDNA could be a useful tool in clinical decision making for patients with EOC. Citation Format: Jocelyn S. Chapman, William E. Pierson, Karen Smith-McCune, Geovanni Pineda, Reena M. Vattakalam, Alexandra Ross, Meredith A. ","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"64 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77935299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-663
Misook Choi, D. Moon, Hae Ung Lee, Jong-min Jo, Young Woong Sohn, B. H. Jeon, Sang-We Kim
{"title":"Abstract 663: Longitudinal AXL assessment of circulating tumor cells (CTCs) and its clinical implication in the patients with EGFR mutated non-small cell lung cancer (NSCLC)","authors":"Misook Choi, D. Moon, Hae Ung Lee, Jong-min Jo, Young Woong Sohn, B. H. Jeon, Sang-We Kim","doi":"10.1158/1538-7445.AM2021-663","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-663","url":null,"abstract":"","PeriodicalId":10518,"journal":{"name":"Clinical Research (Excluding Clinical Trials)","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78304081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-07-01DOI: 10.1158/1538-7445.AM2021-99
S. Suehnholz, Ritika Kundra, Hongxin Zhang, Shaleigh A. Smith, Moriah G. Nissan, Yi-Chen Yao, Lindsay M. LaFave, K. Gala, Linde A. Miles, M. Arcila, M. Ladanyi, M. Berger, A. Zehir, Aijazuddin Syed, J. Rudolph, P. Sabbatini, R. Levine, A. Dogan, Jianjiong Gao, D. Solit, N. Schultz, D. Chakravarty
Genomic sequencing of tumors is a routine part of cancer patient care. To address the need for a comprehensive resource that annotates the oncogenic effects and clinical actionability of somatic alterations in cancer, we developed OncoKB, a precision oncology knowledgebase. Since its introduction in 2016, OncoKB has grown to include annotations for >500 alterations in 682 genes. This includes 42 Level 1 genes (included in the FDA drug label), 12 Level 2 genes (included in the NCCN guidelines), and 29 Level 3A genes (predictive of drug response in well-powered clinical studies). We evaluated changes in the clinical actionability landscape and evolution of the OncoKB annotation rules and processes by comparing the AACR Project GENIE cohort (v8.1) annotated with the OncoKB version from February 2018 to that from November 2020. Even within a short window of time, this comparison reveals a significant shift of the proportion of samples that harbor a standard care alteration (Level 1 and 2), increasing from ~9% in 2018 to ~24% in 2020, and a Level 3A alteration, decreasing from ~11% to ~5%. This shift is partially attributable to the FDA approval of a PI3K inhibitor in PIK3CA-mutant ER+/HER2- breast cancer, approval of RAF inhibitors in BRAF V600E mutant anaplastic thyroid cancer and colorectal cancer, approval of NTRK-inhibitors in NTRK fusion-positive solid tumors, FGFR-inhibitor approval in FGFR2 fusion-positive bladder cancer and cholangiocarcinoma, RET-inhibitor approval in RET fusion-positive thyroid cancer and non-small cell lung cancer and expansion of indications for PARP inhibitors to include prostate cancer. The tumor agnostic approval of the checkpoint blockade inhibitor, pembrolizumab, in TMB-H solid tumors additionally gave rise to a ~4% increase in Level 1 samples. Analysis of the AACR Project GENIE cohort also revealed significant changes to the OncoKB process, including those reflected in the updated OncoKB Levels of Evidence v2.0. The refined levels system deprioritized the significance of standard care biomarkers when present in indications outside of the FDA-approved/NCCN listed indication. This change was based on clinical data demonstrating that patients with investigational predictive biomarkers for a specific tumor type based on compelling clinical evidence from phase 3 trials (currently Level 3A) are more likely to experience clinical benefit compared to patients with predictive biomarkers that are considered standard care in a different tumor type (previously Level 2B, currently Level 3B), and is consistent with guidelines published by ASCO/AMP/CAP and ESMO. Knowledgebases such as OncoKB have emerged as key informational resources that the clinical oncology and scientific communities have used to rapidly connect sequencing results to clinical actionability. Their utility depends on their ability to stay abreast of clinical data and seamlessly adapt their rules and processes to the evolving field of precision medicine. Citation
肿瘤基因组测序是癌症患者护理的常规部分。为了满足对肿瘤中体细胞改变的致瘤效应和临床可操作性的综合资源的需求，我们开发了OncoKB，一个精确的肿瘤学知识库。自2016年推出以来，OncoKB已经发展到包括682个基因中超过500个变化的注释。这包括42个1级基因(包括在FDA药物标签中)，12个2级基因(包括在NCCN指南中)和29个3A级基因(在有力的临床研究中预测药物反应)。通过比较2018年2月至2020年11月使用OncoKB版本注释的AACR Project GENIE队列(v8.1)，我们评估了临床可操作性景观的变化以及OncoKB注释规则和流程的演变。即使在很短的时间窗口内，这一比较也显示了标准护理改变(1级和2级)的样本比例的显著变化，从2018年的~9%增加到2020年的~24%，3A级改变从~11%下降到~5%。这一转变部分归因于FDA批准PI3K抑制剂治疗pik3ca突变型ER+/HER2-乳腺癌，批准RAF抑制剂治疗BRAF V600E突变型间变性甲状腺癌和结直肠癌，批准NTRK抑制剂治疗NTRK融合阳性实体瘤，批准fgfr抑制剂治疗FGFR2融合阳性膀胱癌和胆管癌。RET抑制剂在RET融合阳性甲状腺癌和非小细胞肺癌中的批准，以及PARP抑制剂适应症的扩大，包括前列腺癌。检查点阻断抑制剂派姆单抗(pembrolizumab)在TMB-H实体瘤中的肿瘤诊断性批准也使1级样本增加了约4%。对AACR项目GENIE队列的分析也揭示了OncoKB过程的重大变化，包括更新的OncoKB证据水平v2.0中反映的变化。当标准护理生物标志物出现在fda批准/NCCN列出的适应症以外的适应症时，精炼水平系统会优先考虑其重要性。这一变化是基于临床数据表明，基于3期试验令人信服的临床证据(目前为3A级)，具有特定肿瘤类型研究预测性生物标志物的患者比具有不同肿瘤类型被认为是标准治疗的预测性生物标志物的患者更有可能获得临床获益(以前为2B级，目前为3B级)，并且与ASCO/AMP/CAP和ESMO发布的指南一致。像OncoKB这样的知识库已经成为临床肿瘤学和科学界用来快速将测序结果与临床可操作性联系起来的关键信息资源。他们的效用取决于他们与临床数据保持同步的能力，并无缝地调整他们的规则和流程，以适应不断发展的精准医疗领域。引文格式:Sarah P. Suehnholz, Ritika Kundra，张洪欣，Shaleigh Smith, Moriah Nissan, Yifu Yao, Lindsay LaFave, Kinisha Gala, Linde Miles, Maria E. arcia, Marc Ladanyi, Michael F. Berger, Ahmet Zehir, Aijaz Syed, Julia Rudolph, Paul Sabbatini, Ross Levine, Ahmet Dogan, Jianjiong Gao, David Solit, Nikolaus Schultz, Debyani Chakravarty。精准肿瘤学知识库OncoKB的发展[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志，2021;81(13 -增刊):摘要第99期。
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