Introduction: Population-based datasets are often used to estimate changes in utilization or outcomes of novel therapies. Inclusion or exclusion of unstaged patients may impact on interpretation of these studies.

Methods: A large population-based dataset in Ontario, Canada of non-small cell lung cancer patients was examined to evaluate the characteristics and outcomes of unstaged patients compared to staged patients. Multivariable Poisson regression was used to evaluate differences in patient-level characteristics between groups. Kaplan-Meier estimates of survival and log-rank statistics were utilized.

Results: In our Ontario cohort of 51,152 patients with NSCLC, 11.2% (n=5,707) were unstaged, and there was evidence that stage data was not missing completely at random. Those without assigned stage were more likely than staged patients to be older (RR [95%CI]), (70-79 vs. 20-59: 1.51 [1.38-1.66]; 80+ vs. 20-59: 2.87 [2.62-3.15]), have a higher comorbidity index (Score 1-2 vs 0: 1.19 [1.12-1.27]; 3 vs. 0: 1.49 [1.38-1.60]), and have a lower socioeconomic class (4 vs. 1 (lowest): 0.91 [0.84-0.98]; 5 vs. 1 (lowest): 0.89 [0.83-0.97]). Overall survival of unstaged patients suggested a mixture of early and advanced stage, but with a large proportion that are probably stage IV patients with more rapid death than those with reported stage IV disease.

Conclusion: In this case study, evaluation of stage-specific health care utilization and outcomes for staged patients with stage IV disease at the population level may have a bias as a distinct subset of stage IV patients with rapid death are likely among those without a documented stage in administrative data.

Objective: Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of pulmonary adenocarcinoma that lacks effective treatment. The purpose of this research was to investigate the clinical characteristics, treatment, and prognosis of PEAC, as well as the impact of relevant factors on survival, thus providing a reference for the clinical management of patients with this disease.

Methods: For this study, we gathered clinical data from 26 patients with PEAC in the Affiliated Cancer Hospital of Zhengzhou University from June 2014 to June 2021. We used SEER*Stat software V8.3.5 to download the PEAC patients from the Surveillance, Epidemiology, and End Results (SEER) database. In total, 20 patients were identified. Clinical data, including general information, imaging findings, and treatment protocols, were obtained, together with a follow-up of disease regression. The relevant clinical data were then analyzed.

Results: It included 12 males and 14 females out of 26 patients from China, whose mean age was (62.73 ± 11.89) years; 20 were in the lower lung, 11 were stage I-II, and 15 were stage III-IV. Five had EGFR mutations, and four had KRAS mutations. In terms of treatment, patients with stage I-II were primarily treated by surgery, and patients with stage III-IV were treated mostly by chemotherapy. We extended the follow-up date to January 2022. On completion of the follow-up visit, 11 patients died, and the remaining 15 patients survived. The overall survival (OS) of 26 patients was 2.0-76.0 months, while the mean was 53.1 months, and the median OS (mOS) was 38.0 months (95% CI:1.727-74.273). In the case of progression-free survival (PFS) times, it was 2.0-76.0 months, with a mean PFS of 31.0 months and a median PFS (mPFS) of 8.0 months (95% CI:4.333-11.667). The PFS of the 15 patients in stage III-IV was 2.0-17 months, while the mean PFS was 6.5 months and the mPFS was 6.0 months (95% CI:4.512-7.488). Out of the 20 patients identified in the SEER database, the average age was 69.9 years, with 14 males and 6 females. Of these patients, 8 were diagnosed with stage I-II, while the remaining 11 were diagnosed with stage III-IV. 10 underwent surgery, 4 received radiation therapy, and 9 received chemotherapy. The mean OS of the 20 patients was 67.5 months, mOS was 28.0 months (95% CI: 9.664- 46.336). For patients diagnosed with stage III-IV, the mean OS was 14.8 months and mOS was 20 months (95% CI: 4.713-35.287).

Conclusion: PEAC is rare, and the prognosis is determined mainly by the stage; patients who undergo surgery in stage I-II have a better prognosis.

Background: Afatinib is a potent, irreversible second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor which has demonstrated efficacy in advanced non-small cell lung cancer (NSCLC) patients harboring either common or uncommon EGFR mutations. However, data on its activity against brain metastases are limited. This study aimed to retrospectively evaluate the efficacy and safety of afatinib as first-line treatment for EGFR-mutant NSCLC patients with brain metastases.

Methods: Treatment-naive advanced NSCLC patients harboring EGFR mutations and brain metastases treated with afatinib were retrospectively reviewed to assess the central nervous system (CNS) efficacy and also the systematic benefits.

Results: Totally 43 patients with measurable or non-measurable brain metastases were enrolled in the CNS full analysis (cFAS) set. Among them, 23 patients with measurable brain metastases were included in the CNS evaluable for response (cEFR) set. The CNS ORR was 48.8% (95% CI, 33.3 - 64.5%) in the cFAS set and 82.6% (95% CI, 61.2 - 95.0%) in the cEFR set, respectively. CNS mDoR was 8.9 months (95% CI, 4.7 - 13.1 months) and CNS mPFS was 12.7 months (95% CI, 6.9 - 18.5 months) in the cFAS set. In the subgroup analysis stratified by EGFR mutation types, CNS ORR of cEFR set in the common mutation cohort was 100% (95% CI, 75.3 - 100%) and 60% (95% CI, 26.2 - 87.8%) in the uncommon mutation cohort (p = 0.024); CNS ORR of cFAS set was 57.7% (95% CI, 36.9 - 76.6%) and 35.3% (95% CI, 14.2 - 61.7%), respectively (p = 0.151). CNS mPFS was 14.4 months in patients with common mutations and 6.1 months in patients with uncommon mutations (hazard ratio, 0.47; 95% CI, 0.22 - 1.00; p = 0.045). Patients with common mutations showed a significantly lower cumulative incidence of CNS failure than uncommon mutation cohort (p = 0.0026). Most of patients experienced grade 1/2 treatment-related adverse events.

Conclusions: First-line afatinib demonstrated encouraging efficacy on brain metastases in NSCLC patients harboring either common or major uncommon EGFR mutations in a real-world setting, with manageable toxicities. Patients with common mutations showed better CNS outcomes than those with uncommon mutations.

Background: Genomic profiling of cerebrospinal fluid (CSF) can be used to detect actionable mutations and guide clinical treatment of non-small cell lung cancer (NSCLC) patients with central nervous system (CNS) metastases. Examining the performance of CSF samples in real-world settings can confirm the potential of CSF genotyping for guiding therapy in clinical practice.

Patients and Methods: We included 1,396 samples from 970 NSCLC patients with CNS metastases in real-world settings. All samples underwent targeted next-generation sequencing of 1,021 cancer-relevant genes. In total, 100 CSF samples from 77 patients who had previously received targeted treatment were retrospectively analyzed to explore the mechanisms of TKI-resistance.

Results: For NSCLC patients with CNS metastases, CSF samples were slightly more often used for genomic sequencing in treated patients with only distant CNS metastases compared to other patients (10.96% vs. 0.81–9.61%). Alteration rates in CSF samples were significantly higher than those in plasma, especially for copy number variants (CNV). The MSAFs of CSF samples were significantly higher than those of plasma and tumor tissues (all p <0.001). Remarkably, detection rates of all actionable mutations and EGFR in CSF were higher than those in plasma samples of treated patients (all p <0.0001). For concordance between paired CSF and plasma samples that were simultaneously tested, the MSAF of the CSF was significantly higher than that of matched plasma cfDNA (p <0.001). From multiple comparisons, it can be seen that CSF better detects alterations compared to plasma, especially CNV and structural variant (SV) alterations. CSF cfDNA in identifying mutations can confer the reason for the limited efficacy of EGFR-TKIs for 56 patients (78.87%, 56/71).

Conclusions: This real-world large cohort study confirmed that CSF had higher sensitivity than plasma in identifying actionable mutations and showed high potential in exploring underlying resistance mechanisms. CSF can be used in genomics profiling to facilitate the broad exploration of potential resistance mechanisms for NSCLC patients with CNS metastases.