Estimation of the Percentage of US Patients With Cancer Who Benefit From Genome-Driven Oncology

Marquart, John; Chen, Emerson Y.; Prasad, Vinay

doi:10.1001/jamaoncol.2018.1660

Cited by 297 publications

(242 citation statements)

References 26 publications

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“…These real‐world challenges encountered in our study are well in line with recently published data by Marquart et al ., and underscore the need for clinical trials on targeted therapies in CUP as exemplified by the currently recruiting phase II CUPISCO trial (http://clinicaltrials.gov Identifier: NCT03498521), which grants access to targeted therapies, incorporates newly emerging molecular therapies by amendments and targets patients with good ECOG performance status early on in first‐line treatment.…”

Section: Discussionsupporting

confidence: 79%

Integrated clinicomolecular characterization identifies RAS activation and CDKN2A deletion as independent adverse prognostic factors in cancer of unknown primary

Bochtler

Reiling

Endris

et al. 2020

Intl Journal of Cancer

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Cancer of unknown primary (CUP) denotes a malignancy with histologically confirmed metastatic spread while the primary tumor remains elusive. Here, we address prognostic and therapeutic implications of mutations and copy number variations (CNVs) detected in tumor tissue in the context of a comprehensive clinical risk assessment. Targeted panel sequencing was performed in 252 CUP patients. 71.8% of patients had unfavorable CUP according to ESMO guidelines. 74.7% were adeno‐ and 13.7% squamous cell carcinomas. DNA was extracted from microdissected formalin‐fixed, paraffin‐embedded tissues. For library preparation, mostly multiplex PCR‐based Ion Torrent AmpliSeq™ technology with Oncomine comprehensive assays was used. Most frequent genetic alterations were mutations/deletions of TP53 (49.6%), CDKN2A (19.0%) and NOTCH1 (14.1%) as well as oncogenic activation of KRAS (23.4%), FGFR4 (14.9%) and PIK3CA (10.7%). KRAS activation was predominantly found in adenocarcinomas (p = 0.01), PIK3CA activation in squamous cell carcinomas (p = 0.03). Male sex, high ECOG score, unfavorable CUP, higher number of involved organs and RAS activation predicted decreased event‐free and overall survival in multivariate analysis. Deletions of CDKN2A were prognostically adverse regarding overall survival. TP53 mutations did not significantly influence prognosis in the overall cohort, but worsened prognosis in otherwise favorable CUP subtypes. Although not standard in CUP, for 17/198 (8.6%) patients molecularly targeted treatment was recommended and 10 patients (5.1%) were treated accordingly. In conclusion, besides the identification of drug targets, panel sequencing in CUP is prognostically relevant, with RAS activation and CDKN2A deletion emerging as novel independent risk factors in a comprehensive assessment with clinicopathological data.

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Section: Discussionsupporting

confidence: 79%

Integrated clinicomolecular characterization identifies RAS activation and CDKN2A deletion as independent adverse prognostic factors in cancer of unknown primary

Bochtler

Reiling

Endris

et al. 2020

Intl Journal of Cancer

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“…Instead, the authors used the year of diagnosis as a proxy for receipt of newly approved cancer treatments. Use of the date of diagnosis as a proxy for receipt of cancer treatment is especially problematic for immunotherapy, for which only small percentages of patients are eligible …”

Section: Changes In Receipt Of Systemic Treatment For Select Cancers mentioning

confidence: 99%

Data challenges for evaluating new treatments

Nogueira

Yabroff

Siegel

et al. 2019

Cancer

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“…Personalized or Precision Medicine [13], which purports to account for individualindividual variability in the clinical setting by attempting to identify particular patientdisease characteristics associated with improved responsiveness to existing drugs or other treatment modalities. This process is most notably applied in the area of oncology, where tumor genotypes are correlated with presumptively more effective drug combinations (though it is apparent that, based on existing efficacy and applicability, this approach is still in evolution [14]). …”

Section: Introductionmentioning

confidence: 99%

The Crisis of Reproducibility, the Denominator Problem and the Scientific Role of Multi-Scale Modeling

An¹

2018

Preprint

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Abstract:The "Crisis of Reproducibility" has received considerable attention both within the scientific community and without. While factors associated with scientific culture and practical practice are most often invoked, I propose that the Crisis of Reproducibility is ultimately a failure of generalization with a fundamental scientific basis in the methods used for biomedical research. The Denominator Problem describes how limitations intrinsic to the two primary approaches of biomedical research, clinical studies and preclinical experimental biology, lead to an inability to effectively characterize the full extent of biological heterogeneity, which compromises the task of generalizing acquired knowledge. Drawing on the example of the unifying role of theory in the physical sciences, I propose that multi-scale mathematical and dynamic computational models, when mapped to the modular structure of biological systems, can serve a unifying role as formal representations of what is conserved and similar from one biological context to another. This ability to explicitly describe the generation of heterogeneity from similarity addresses the Denominator Problem and provides a scientific response to the Crisis of Reproducibility. Preprints (www.preprints.org) | NOT PEER-REVIEWED |

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Estimation of the Percentage of US Patients With Cancer Who Benefit From Genome-Driven Oncology

Cited by 297 publications

References 26 publications

Integrated clinicomolecular characterization identifies RAS activation and CDKN2A deletion as independent adverse prognostic factors in cancer of unknown primary

Integrated clinicomolecular characterization identifies RAS activation and CDKN2A deletion as independent adverse prognostic factors in cancer of unknown primary

Data challenges for evaluating new treatments

The Crisis of Reproducibility, the Denominator Problem and the Scientific Role of Multi-Scale Modeling

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