Universal CGP in Lung Cancer: Comparing MENG (2024) and DOWDELL (2024)

 See a discussion of DOWDELL at ASCO Daily News.

https://dailynews.ascopubs.org/do/comprehensive-genomic-profiling-improves-precision-therapy-use-and-patient-survival

Here are the citations to MENG and to DOWDELL.  MENG looks at CGP in lung cancer, DOWDELL looks at CGP across solid cancers.

Here are the citations for each paper in a standard format:

1. Meng, R., Dowdell, A. K., Vita, A., Hanes, D., Bapat, B., Chang, S.-C., Harold, L., Schmidt, M., Wong, C., Poon, H., Schroeder, B., Weerasinghe, R., Sanborn, R., Leidner, R., Urba, W. J., Bifulco, C., & Piening, B. (2024). Clinical impact for advanced non-small-cell lung cancer patients tested using comprehensive genomic profiling at a large USA health care system. ESMO Real World Data and Digital Oncology, Volume 5, Issue C. https://doi.org/10.1016/j.esmorw.2024.100057.

2. Dowdell, A. K., Meng, R. C., Vita, A., Bapat, B., Hanes, D., Chang, S.-C., Harold, L., Wong, C., Poon, H., Schroeder, B., Weerasinghe, R., Leidner, R., Urba, W. J., Bifulco, C., & Piening, B. D. (2024). Widespread adoption of precision anticancer therapies after implementation of pathologist-directed comprehensive genomic profiling across a large US health system. JCO Oncology Practice, 20(11), 1523-1532. https://doi.org/10.1200/OP.24.00226.

Here is an AI comparision of the two papers.

The two studies by Meng et al. and Dowdell et al. focus on the clinical impact of comprehensive genomic profiling (CGP) for cancer patients, particularly in non-small cell lung cancer (NSCLC) and advanced solid tumors, using Providence Health System’s in-house CGP protocol. Here’s a PhD-level comparative analysis and overlap assessment:

1. Research Context and Objectives:
   Both studies aim to assess the effectiveness of in-house CGP on treatment outcomes and precision therapy adoption. Meng et al. focus specifically on advanced NSCLC patients, comparing outcomes between CGP-tested patients and those using a prior 50-gene small panel. Dowdell et al. take a broader approach by implementing pathologist-directed CGP testing across various tumor types and stages, with an emphasis on precision therapy adoption and overall survival benefits.

2. Methodology and Cohorts:

   • Meng et al. assess NSCLC patients with a targeted comparison between those tested with CGP versus a prior small panel, concentrating on actionable biomarker detection and therapy alignment. Their CGP panel (ProvSeq 523 genes) was implemented to capture actionable mutations, especially in NSCLC, using a structured approach with additional PD-L1 and TMB biomarker analysis.
   • Dowdell et al., by contrast, standardize CGP testing across all advanced cancers in a broader patient cohort (3,216 cases), with a focus on universal adoption through a pathologist-directed protocol immediately at diagnosis. They also explore clinical trial eligibility as a metric for treatment efficacy. While both studies use the same CGP panel, Dowdell’s study includes a broader in silico comparator cohort to estimate outcomes based on a 50-gene panel.

3. Data Collection and Analysis Techniques:
   Both studies employ natural language processing (NLP) tools to extract PD-L1 results from pathology notes, achieving high precision and recall, which enhances consistency in biomarker reporting.   However, Dowdell et al. adopt additional machine-learning-based chart mining across a more diverse tumor registry dataset, thus allowing for a more comprehensive analysis of various tumor types and treatment modalities.

4. Results – Actionable Biomarkers and Therapy Outcomes:

   • In Meng et al., CGP testing led to actionable biomarkers in 77% of NSCLC cases, with a significant survival advantage (median OS of 15.7 months for CGP versus 7 months for small panel). CGP testing increased precision therapy usage from 50% to 64%, with a higher rate of TT utilization.
   • Dowdell et al. report that 49% of all advanced cancer cases had at least one actionable biomarker, and CGP expanded eligibility for precision therapy by broadening access to trials. They found that CGP-tested patients with actionable markers had a 52% rate of TT or IO usage, with improved OS (25 months for TT versus 17 months for chemotherapy alone).

5. Overlap and Novel Contributions:
   Both studies overlap in highlighting CGP’s value in expanding treatment options and survival outcomes. However, Meng et al. provide a narrower focus on NSCLC and the CGP panel’s ability to detect mutations previously missed by small panels. Dowdell et al. expand this by applying CGP across a diverse range of cancers and emphasizing a system-wide protocol that standardizes CGP from the diagnostic stage, aiming to reduce barriers to testing and improve workflow efficiency.

6. Conclusions and Implications:
   Both papers underscore CGP’s efficacy in promoting precision medicine and improving patient survival. Meng et al.’s findings are particularly compelling for NSCLC clinical protocols, while Dowdell et al. suggest that pathologist-directed CGP testing could become a standard in cancer care, highlighting broader, system-level changes in oncology practice.

In summary, the studies provide complementary perspectives, with Meng et al. focused on deep insights into NSCLC patient outcomes, and Dowdell et al. highlighting systemic protocol shifts and broader population impacts. This synthesis supports the push toward CGP standardization in oncology but points to specific improvements in protocol, turnaround time, and physician engagement to achieve widespread, effective CGP implementation.