The role of combination chemotherapy with immune checkpoint inhibitors (ICI) (ICI-chemo) over ICI monotherapy (ICI-mono) in non-small cell lung cancer (NSCLC) remains underexplored. In this retrospective study of 1133 NSCLC patients, treatment with ICI-mono vs ICI-chemo associate with higher rates of early progression, but similar long-term progression-free and overall survival. Sequential vs concurrent ICI and chemotherapy have similar long-term survival, suggesting no synergism from combination therapy. Integrative modeling identified PD-L1, disease burden (Stage IVb; liver metastases), and STK11 and JAK2 alterations as features associate with a higher likelihood of early progression on ICI-mono. CDKN2A alterations associate with worse long-term outcomes in ICI-chemo patients. These results are validated in independent external (n = 89) and internal (n = 393) cohorts. This real-world study suggests that ICI-chemo may protect against early progression but does not influence overall survival, and nominates features that identify those patients at risk for early progression who may maximally benefit from ICI-chemo.
Quantitative reasoning in medical decision science relies on the delineation of pathological objects. For example, evidence‐based clinical decisions regarding lung diseases require the segmentation of nodules, tumors, or cancers. Non‐small cell lung cancer (NSCLC) tends to be large sized, irregularly shaped, and grows against surrounding structures imposing challenges in the segmentation, even for expert clinicians. An automated delineation tool based on spatial analysis was developed and studied on 25 sets of computed tomography scans of NSCLC. Manual and automated delineations were compared, and the proposed method exhibited robustness in terms of the tumor size (5.32–18.24 mm), shape (spherical or irregular), contouring (lobulated, spiculated, or cavitated), localization (solitary, pleural, mediastinal, endobronchial, or tagging), and laterality (left or right lobe) with accuracy between 80% and 99%. Small discrepancies observed between the manual and automated delineations may arise from the variability in the practitioners' definitions of region of interest or imaging artifacts that reduced the tissue resolution.
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