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Non-Small-cell lung cancer case series

Qin et al. conducted a retrospective study of patients with mNSCLC treated with ICIs at 2 tertiary care centers from 2014 through 2017. Overall survival (OS) was compared between patients with and without baseline bone metastases using a log-rank test. A Cox regression model was used to evaluate the association between OS and the presence of bone metastases at ICI initiation, controlling for other confounding factors.

Results: We identified a cohort of 330 patients who had received ICIs for metastatic disease. Median patient age was 63 years, most patients were treated in the second line or beyond (n=259; 78%), and nivolumab was the most common ICI (n=211; 64%). Median OS was 10 months (95% CI, 8.4-12.0). In our cohort, 124 patients (38%) had baseline bone metastases, and 43 (13%) developed SREs during or after ICI treatment. Patients with bone metastases had a higher hazard of death after controlling for performance status, histology, line of therapy, and disease burden (hazard ratio, 1.57; 95% CI, 1.19-2.08; P=.001). Use of BMAs was not associated with OS or a decreased risk of SREs.

Conclusions: Presence of bone metastases at baseline was associated with a worse prognosis for patients with Non-Small-cell lung cancer treated with Immune Checkpoint Inhibitor after controlling for multiple clinical characteristics. Use of bone-modifying agents (BMAs) was not associated with reduced skeletal-related events (SREs) or a difference in survival 1).

prospectively enrolled patients with EGFR-mutant NSCLC who underwent CSF sampling for suspected LM. The supernatant of CSF after routine cytology examination was collected. The diagnosis of LM was established according to EANO-ESMO criteria. CSF and plasma cell-free DNA (cfDNA) were retrieved for EGFR mutation testing.

Results: Fifty-one patients with a median age of 62.7 years were enrolled. The median duration from initial diagnosis to CSF sampling was 23.0 months and most patients (94.1%) had received at least one EGFR-tyrosine kinase inhibitor. Adenocarcinoma cells were found in 37 CSF samples (72.5%), and 48 (94.1%) patients had confirmed or probable LM. Thirty-five of these 48 patients (72.9%) had valid EGFR mutation-testing results using CSF cfDNA and tended to have higher white blood cell counts and positive cytology in their CSF compared to those with invalid mutation testing results. The overall detection rate of EGFR mutation in CSF cfDNA was 68.8%, and the T790M detection rate was 14.6%. In 37 patients with paired CSF and plasma samples, the concordance rate of the EGFR mutation results was 29.7%.

For patients with EGFR-mutant NSCLC with LM, CSF supernatant is a valuable source for EGFR mutation testing and may provide important information 2).

Of 802 patients with non-Small-cell lung cancer who underwent primary staging by a single-day protocol of whole-body PET/CT plus brain PET/MR, 72 cases with adenocarcinoma and brain metastases were enrolled for a prognostic analysis of OS. On the basis of the available follow-up brain status, only 52 patients were eligible for prognostic analysis of nTTP. Metastatic brain tumors were identified on post-contrast MR imaging, and the tumor-to-brain ratio (TBR) was measured on PET images.

Multivariate analysis revealed that FDG-PET findings and eligibility for initial treatment with targeted therapy were significant independent predictors of nTTP and OS. A new index, termed the molecular imaging prognostic (MIP) score, was proposed to define three disease classes. MIP scores were significant predictors of both nTTP and OS (P < 0.001). Pre-existing prognostic indices such as Lung-molGPA scores were significant predictors of OS but did not predict nTTP.

When staging is performed with whole-body PET/CT plus brain PET/MR, this new prognostic index may be helpful to stratify the outcomes of patients with lung adenocarcinoma and brain metastases. The superior prognostic power of this index for nTTP might be used to select appropriate patients for intracranial control and thereby achieve better quality of life 3).

Consecutive patients with advanced NSCLC who attended Kindai University Hospital between January 2007 and January 2016 were recruited to this retrospective study. Patients with regional lymph node-negative disease and a limited number of metastatic lesions (≤5) per organ site and a limited number of affected organ sites (1 or 2) were eligible.

Eighteen patients were identified for analysis during the study period. The most frequent metastatic site was the central nervous system (CNS, 72%). Most patients (83%) received systemic chemotherapy, with only three (17%) undergoing surgery, for the primary lung tumor. The CNS failure sites for patients with CNS metastases were located outside of the surgery or radiosurgery field. The median overall survival for all patients was 15.9 months, with that for EGFR mutation-positive patients tending to be longer than that for EGFR mutation-negative patients.

Cure is difficult to achieve with current treatment strategies for NSCLC patients with synchronous oligometastases, although a few long-term survivors and a smaller number of patients alive at last follow-up were present among the study cohort. There is an urgent clinical need for prospective evaluation of surgical resection as a treatment for oligometastatic NSCLC, especially negative for driver mutations 4).

Qin A, Zhao S, Miah A, Wei L, Patel S, Johns A, Grogan M, Bertino EM, He K, Shields PG, Kalemkerian GP, Gadgeel SM, Ramnath N, Schneider BJ, Hassan KA, Szerlip N, Chopra Z, Journey S, Waninger J, Spakowicz D, Carbone DP, Presley CJ, Otterson GA, Green MD, Owen DH. Bone Metastases, Skeletal-Related Events, and Survival in Patients With Metastatic Non-Small-cell lung cancer Treated With Immune Checkpoint Inhibitors. J Natl Compr Canc Netw. 2021 Apr 20:1-7. doi: 10.6004/jnccn.2020.7668. Epub ahead of print. PMID: 33878726.
Chiang CL, Lee CC, Huang HC, Wu CH, Yeh YC, Shen CI, Luo YH, Shiao TH, Chang HJ, Huang YT, Chen YM, Chou TY, Chiu CH. Utility of Cerebrospinal Fluid Cell-Free DNA in Patients with EGFR-Mutant Non-Small-Cell Lung Cancer with Leptomeningeal Metastasis. Target Oncol. 2021 Feb 10. doi: 10.1007/s11523-021-00791-9. Epub ahead of print. PMID: 33566300.
Ho KC, Toh CH, Li SH, Liu CY, Yang CT, Lu YJ, Su TP, Wang CW, Yen TC. Prognostic impact of combining whole-body PET/CT and brain PET/MR in patients with lung adenocarcinoma and brain metastases. Eur J Nucl Med Mol Imaging. 2018 Nov 10. doi: 10.1007/s00259-018-4210-1. [Epub ahead of print] PubMed PMID: 30415280.
Sakai K, Takeda M, Hayashi H, Tanaka K, Okuda T, Kato A, Nishimura Y, Mitsudomi T, Koyama A, Nakagawa K. Clinical outcome of node-negative oligometastatic non-Small-cell lung cancer. Thorac Cancer. 2016 Sep 12. doi: 10.1111/1759-7714.12386. PubMed PMID: 27755813.
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