Daily Respiratory Research Analysis
Three studies stand out today: a preplanned phase 3 analysis shows serum VEGF-A can identify metastatic NSCLC patients who benefit from adding bevacizumab to chemo-immunotherapy; a nationwide Rwandan study demonstrates that Xpert MTB/RIF Ultra yields a high rate of false rifampicin resistance in very low bacillary-load samples, calling for confirmatory testing; and a multicenter single-arm trial (CRES) reports strong 3-year survival with S-1+cisplatin chemoradiation followed by surgery for super
Summary
Three studies stand out today: a preplanned phase 3 analysis shows serum VEGF-A can identify metastatic NSCLC patients who benefit from adding bevacizumab to chemo-immunotherapy; a nationwide Rwandan study demonstrates that Xpert MTB/RIF Ultra yields a high rate of false rifampicin resistance in very low bacillary-load samples, calling for confirmatory testing; and a multicenter single-arm trial (CRES) reports strong 3-year survival with S-1+cisplatin chemoradiation followed by surgery for superior sulcus lung cancer.
Research Themes
- Biomarker-guided precision therapy in lung cancer
- Diagnostic stewardship for drug-resistant tuberculosis
- Optimization of trimodality treatment for superior sulcus lung cancer
Selected Articles
1. Serum VEGF-A as a biomarker for the addition of bevacizumab to chemo-immunotherapy in metastatic NSCLC.
In a preplanned biomarker analysis within a phase 3 trial (APPLE), baseline serum VEGF-A (and isoforms) measured by ELISA identified metastatic nonsquamous NSCLC patients who derived significant PFS benefit from adding bevacizumab to atezolizumab plus platinum chemotherapy. The work supports serum VEGF-A as a practical predictive biomarker for tailoring anti-VEGF use with chemo-immunotherapy.
Impact: Provides a clinically actionable biomarker to personalize bevacizumab use with chemo-immunotherapy in metastatic NSCLC, potentially improving outcomes and minimizing toxicity/costs.
Clinical Implications: Consider baseline serum VEGF-A testing to guide adding bevacizumab to atezolizumab plus platinum chemotherapy; patients with low VEGF-A appear to gain PFS benefit. Validation and cutoff standardization are needed before routine adoption.
Key Findings
- Baseline low serum VEGF-A identified patients with significant PFS benefit from adding bevacizumab to atezolizumab + platinum chemotherapy.
- VEGF-A and its isoforms can be quantified via ELISA, enabling practical implementation.
- Preplanned analysis within a phase 3 RCT supports VEGF-A as a predictive (not merely prognostic) biomarker for anti-VEGF add-on.
Methodological Strengths
- Preplanned biomarker analysis embedded in a phase 3 randomized trial
- Standardized ELISA measurements at baseline with clinically relevant endpoint (PFS)
Limitations
- Biomarker groups were not randomized; potential residual confounding
- Findings derived from a single trial dataset without external validation or prespecified universal cutoffs
Future Directions: Conduct prospective biomarker-enriched or biomarker-stratified RCTs, define and validate universal VEGF-A/isoform cutoffs, and assess cost-effectiveness and OS benefit.
2. Paucibacillary Tuberculosis Drives the Low Positive Predictive Value of Xpert MTB/RIF Ultra for Rifampicin Resistance Detection in Low-Prevalence Settings.
In Rwanda, only 32% of Xpert Ultra RR-TB calls were confirmed on repeat testing; among samples with very low bacillary load, 89% of RR calls were false, yielding substantial overtreatment. Programs should confirm RR-TB detected at very low bacillary load (e.g., via repeat Ultra, rpoB sequencing, or pDST) and adjust algorithms accordingly.
Impact: Directly informs global TB diagnostic algorithms to prevent unnecessary RR-TB treatment when Ultra indicates resistance at very low bacillary load.
Clinical Implications: When Ultra reports rifampicin resistance with very low bacillary load, require confirmatory testing before initiating RR-TB regimens. Implement repeat Ultra and, where feasible, rpoB sequencing and pDST to improve PPV.
Key Findings
- Only 32% (41/129) of initial Ultra RR-TB calls were concordant on repeat Ultra testing.
- Among 'very low' bacillary load samples, 89% had false RR results (risk ratio 8.20; 95% CI 3.56–18.85).
- Overall, 53% (54/101) of patients with reference testing received unnecessary RR-TB treatment due to false resistance calls.
Methodological Strengths
- Nationwide real-world cohort with repeat Ultra plus rpoB sequencing and phenotypic DST as reference
- Quantified effect of bacillary load categories on false resistance risk
Limitations
- Reference testing was not available for all unconfirmed cases, introducing potential verification bias
- Single-country setting may limit generalizability to other epidemiologic contexts
Future Directions: Develop and validate diagnostic algorithms that incorporate bacillary load thresholds to trigger confirmatory testing; assess cost-effectiveness and patient outcomes of revised workflows.
3. CRES
In the multicenter single-arm CRES trial for superior sulcus NSCLC, induction S-1+cisplatin with concurrent 66 Gy radiotherapy followed by surgery achieved ORR 42%, pCR 33%, and 3-year OS/PFS of 73.2%/53.3%. Local control was excellent, with relapse dominated by distant metastases, supporting this trimodality approach as a potential standard.
Impact: Provides confirmatory multicenter data supporting a specific induction CRT regimen (S-1+cisplatin, 66 Gy) plus surgery for superior sulcus NSCLC with high 3-year survival.
Clinical Implications: For fit patients with superior sulcus NSCLC, consider induction S-1+cisplatin with concurrent 66 Gy radiotherapy followed by surgery. Vigilance for distant relapse is warranted, suggesting a role for optimized systemic therapy and surveillance.
Key Findings
- Objective response rate 42% and pathological complete response rate 33% after S-1+cisplatin CRT followed by surgery.
- Three-year overall survival 73.2% and progression-free survival 53.3%.
- Relapses were predominantly distant metastases; treatment-related deaths occurred in two during induction (pneumonia) and one postoperative (cardiac arrest).
Methodological Strengths
- Multicenter confirmatory design with standardized radical-dose radiotherapy (66 Gy)
- Use of hard clinical endpoints including pCR, OS, and PFS
Limitations
- Single-arm design without randomized comparator limits causal inference
- Generalizability beyond participating centers and populations requires caution
Future Directions: Compare this regimen against other induction CRT backbones in randomized trials; evaluate systemic therapy intensification or consolidation to reduce distant relapse.