Spine Metastasis Is Associated with the Development of Brain Metastasis in Non-Small-Cell Lung Cancer Patients.

Background and Objectives: The mechanisms involved in the development of brain metastasis (BM) remain elusive. Here, we investigated whether BM is associated with spine involvement in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: A consecutive 902 patients with metastatic NSCLC were included from the Inha Lung Cancer Cohort. Patients with BM at diagnosis or subsequent BM development were evaluated for both spine involvement in NSCLC and anatomic proximity of BM to the cerebrospinal fluid (CSF) space. Results: At diagnosis, BM was found in 238 patients (26.4%) and bone metastasis was found in 393 patients (43.6%). In patients with bone metastasis, spine involvement was present in 280 patients. BM subsequently developed in 82 (28.9%) of 284 patients without BM at diagnosis. The presence of spine metastasis was associated with BM at diagnosis and subsequent BM development (adjusted odd ratios and 95% confidence intervals = 2.42 and 1.74-3.37, p < 0.001; 1.94 and 1.19-3.18, p = 0.008, respectively). Most patients with spine metastasis, either with BM at diagnosis or subsequent BM, showed BM lesions located adjacent (within 5mm) to the CSF space (93.8% of BM at the diagnosis, 100% of subsequent BM). Conclusions: These findings suggest that the presence of spine involvement is a risk factor for BM development in NSCLC patients with bone metastasis.

Usefulness of bronchial washing fluid for detection of EGFR mutations in non-small cell lung cancer.

INTRODUCTION: The implementation of bronchial washing fluid (BWF) as a diagnostic specimen may complement the low diagnostic yields of plasma in detecting EGFR mutation (mEGFR) in non-small cell lung cancer. However, the diagnostic value of BWF in detecting mEGFR has yet to be clarified. MATERIALS AND METHODS: From March 2021 to August 2022, patients with histologically confirmed NSCLC with matched tumor tissue, BWF, and/or plasma samples were enrolled. Patients were classified into either initial diagnosis or rebiopsy groups. Diagnostic yields of mEGFR in BWF and plasma were evaluated using droplet digital polymerase chain reaction and compared to mEGFR in tumor tissue as standard. RESULTS: The study included 123 patients (74.1 %) in the initial diagnosis and 43 patients (25.9 %) in the rebiopsy group. BWF showed higher sensitivity, specificity, and concordance rates than plasma in both the initial diagnosis (57.4 %, 96.4 %, and 74.0 % vs. 16.4 %, 96.2 %, and 53.1 %) and the rebiopsy group (87.9 %, 60.0 %, and 81.4 % vs. 25.0 %, 75.0 %, and 41.7 %). In the initial diagnosis group, mEGFR was detected in the BWF of 13 out of 16 patients, even in the absence of tumor cells in the tissue biopsy. In these cases, EGFR test results obtained from BWF showed concordance with EGFR test results from the tumor tissue obtained through repeated biopsy or surgery later. In the rebiopsy group, T790M was detected in 16 patients (37.2 %) by tissue biopsy. The combined use of tissue biopsy and BWF increased detection, confirming T790M in 22 patients (51.2 %). DISCUSSION: The detection of mEGFR using BWF shows higher diagnostic yields than plasma for both initial diagnosis and rebiopsy. T790M was detected earlier in BWF than in tissue rebiopsy in some cases, providing patients with an early opportunity to access third-generation EGFR-TKIs. The complementary use of BWF with tumor tissue may improve precision in EGFR-mutated NSCLC treatment strategies.

Incidence and associated risk factors of nontuberculous mycobacterial infection in patients with depression.

BACKGROUND: It has been reported that the risk of mental health problems such as anxiety or depression increases in patients with nontuberculous mycobacterial (NTM) infection. However, no studies have investigated whether the incidence of NTM infection increases in patients with depression. This study aimed to investigate the incidence of NTM infection in patients with depression and evaluate the association between NTM infection and depression stratified by age and sex. METHODS: Data from 2002 to 2013 were collected from patients aged ≥ 20 years in the National Health Insurance Service-National Sample Cohort database. Patients with and without depression aged over 20 years were matched with 1 to 4 by sex, age, and year of diagnosis. The incidence rate was calculated in 100,000 person-years, and a multivariable subdistribution hazard model was used to evaluate the adjusted hazard ratio (aHR) for the development of NTM infection. RESULTS: We included 37,554 individuals (12,752 men and 24,802 women) and 149,213 controls in the depression and non-depression groups, respectively. The cumulative incidence of NTM infection did not differ significantly between the depression and non-depression groups during the follow-up period (22.2 vs. 24.5 per 100,000 person-years, p = 0.571). The age- and sex-stratified effects on the incidence of NTM infection were not significantly higher in patients with depression than in those without depression. After adjusting for covariates including age, sex, comorbidity, income, and region, the risk of NTM infection did not significantly differ between the depression and non-depression groups (aHR 0.83, 95% confidence interval 0.58-1.17). CONCLUSION: The incidence of NTM infections in patients with depression was not significantly higher than that in patients without depression. However, due to the small number of NTM infections, we might have underestimated the differences between the two groups. Further studies are needed to identify factors associated with NTM pulmonary disease in patients with depression.

Effect of whole-brain radiotherapy with platinum-based chemotherapy in non-small cell lung cancer patients with multiple metastases including brain metastases.

Current guidelines recommend that cytotoxic chemotherapy be considered first in non-small cell lung cancer (NSCLC) patients with multiple metastases, and whole-brain radiotherapy (WBRT) is not initially recommended even if brain metastases are present. However, cytotoxic chemotherapeutic agents are less effective in brain metastases due to poor blood-brain barrier permeability. We investigated the effect of WBRT in combination with cytotoxic chemotherapy on survival in NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases. From January 2005 to December 2018, histologically confirmed NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases were included in this study. Patients were classified into two groups based on receiving WBRT prior to or concurrently with administration of first-line chemotherapeutic agents or receiving chemotherapy only. We compared intracranial progression-free survival (iPFS) and overall survival (OS). Of the 240 NSCLC patients with brain metastases at diagnosis and an ECOG PS of 2, 67 patients were EGFR, ALK, and PD-L1 negative with multiple metastases including brain metastases. Among those patients, 43 (64.2%) received WBRT prior to or concurrently with platinum-based chemotherapy. Patients who received WBRT prior to or concurrently with chemotherapy had better iPFS (7.7 months [4.8-10.6] vs. 3.5 months [2.1-4.9], p = 0.009) and OS (10.8 months [5.9-15.7] vs. 6.1 months [1.9-10.3], p = 0.038) than those who did not receive WBRT. In multivariate analyses, WBRT was significantly associated with iPFS (HR: 1.94 and 95% CI 1.11-3.40, p = 0.020) and OS (HR: 1.92 and 95% CI 1.08-3.42, p = 0.027). In NSCLC patients who are EGFR, ALK, and PD-L1 negative, have an ECOG PS of 2, and have multiple metastases including brain metastases, WBRT prior to or concurrently with chemotherapy could improve iPFS and OS. Therefore, the combination of WBRT with cytotoxic chemotherapy should be considered in these patients.

Efficacy of crizotinib retreatment after crizotinib-related interstitial lung disease in a patient with ROS1-rearranged advanced lung adenocarcinoma: A case report and potential crizotinib retreatment strategy.

Crizotinib is an oral selective small-molecular tyrosine kinase inhibitor (TKI) that suppress the activity of anaplastic lymphoma kinase (ALK) and ROS1 kinases, as well as mesenchymal-epithelial transition. The cumulative clinical trials in patients with advanced ALK- or ROS1-rearrangement NSCLC indicate that crizotinib has significant antitumor activity and a tolerable safety profile, with mild or moderate adverse events of visual disorders, diarrhea, nausea, and vomiting. As with other TKIs, however, the occurrence of crizotinib-related interstitial lung disease (crizotinib-ILD) remains a major clinical dilemma that can lead to the permanent discontinuation of TKI during cancer treatment. When there is no suitable alternative therapy for patients who develop crizotinib-ILD, some clinicians have reported successful crizotinib retreatment in cases of ALK-rearrangement NSCLC. Unfortunately, there are no specific guidelines for the treatment or retreatment of TKI-related ILD. We herein report the first successful crizotinib retreatment after crizotinib-ILD in a patient with ROS1-rearranged NSCLC, and suggest a retreatment strategy after crizotinib-ILD based on a literature review.

Monitoring Circulating Tumor DNA in Untreated Non-Small-Cell Lung Cancer Patients.

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.

A Preliminary Study on the Prognostic Impact of Neutrophil to Lymphocyte Ratio of the Bronchoalveolar Lavage Fluid in Patients with Lung Cancer.

The cumulative results indicate that the neutrophil to lymphocyte ratio of peripheral blood (pbNLR) is a useful prognostic factor in patients with various cancers. In contrast to peripheral blood, the bronchoalveolar lavage (BAL) fluid is in direct contact with the lung lesion. However, no study has reported on the clinical utility of the NLR of BAL fluid (bNLR) for patients with lung cancer. To investigate the clinical utility of the bNLR as a prognostic factor in patients with lung cancer, we conducted a retrospective review of the prospectively collected data. A total of 45 patients were classified into high bNLR (n = 29) and low bNLR (n = 16) groups. A high pbNLR and high bNLR were associated with a shorter overall survival (p < 0.001 and p = 0.011, respectively). A multivariable analysis confirmed that ECOG PS (p = 0.023), M stage (p = 0.035), pbNLR (p = 0.008), and bNLR (p = 0.0160) were independent predictors of overall survival. Similar to the pbNLR, a high bNLR value was associated with a poor prognosis in patients with lung cancer. Although further studies are required to apply our results clinically, this is the first study to show the clinical value of the bNLR in patients with lung cancer.

Heterogeneous radiological response to chemotherapy is associated with poor prognosis in advanced non-small-cell lung cancer.

BACKGROUND: A heterogeneous radiological response is frequently observed in cancer patients and could reflect tumor heterogeneity. We investigated the prognostic impact of heterogeneous radiological responses in patients with advanced non-small-cell lung cancer (NSCLC) who received platinum-based chemotherapy. METHODS: The treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria was evaluated in 212 patients with advanced NSCLC who received platinum-based chemotherapy. Patients with partial response (PR) or stable disease (SD) were classified into "PR homo," "PR hetero," "SD homo," and "SD hetero" by the presence of a heterogeneous radiological response, and survival was compared between groups. We also compared survival based on the presence of metabolic responses in lesions with heterogeneous radiological responses. RESULTS: Fifty-two patients (24.5%) were classified as PR, 112 patients (52.8%) as SD, and 48 patients (22.7%) as progressive disease (PD). There was no significant difference in progression-free survival (PFS) and overall survival (OS) between the PR homo and PR hetero groups. The SD homo group had a longer PFS and OS than the SD hetero group. In the SD hetero group, patients with increased maximum standardized uptake value (SUVmax) in lesions with heterogeneous radiological responses had a shorter PFS than those with a stable SUVmax. CONCLUSIONS: The presence of lesions with radiological heterogeneity was associated with disease progression and poor prognosis in the SD group. Patients with heterogeneous radiological responses require careful monitoring.

Smoking and Flap Survival.

PURPOSE: The aim of this study was to compare the complications of flap surgery in non-smokers and smokers and to determine how the incidence of complications was affected by the abstinence period from smoking before and after flap surgery. METHODS: In PubMed and Scopus, terms "smoking" and "flap survival" were used, which resulted in 113 papers and 65 papers, respectively. After excluding 6 duplicate titles, 172 titles were reviewed. Among them, 45 abstracts were excluded, 20 full papers were reviewed, and finally 15 papers were analyzed. RESULTS: Post-operative complications such as flap necrosis (P < .001), hematoma (P < .001), and fat necrosis (P = .003) occurred significantly more frequently in smokers than in non-smokers. The flap loss rate was significantly higher in smokers who were abstinent for 24 hours post-operatively than in non-smokers (n = 1464, odds ratio [OR] = 4.885, 95% confidence interval [CI] = 2.071-11.524, P < .001). The flap loss rate was significantly lower in smokers who were abstinent for 1 week post-operatively than in those who were abstinent for 24 hours post-operatively (n = 131, OR = 0.252, 95% CI = 0.074-0.851, P = .027). No significant difference in flap loss was found between non-smokers and smokers who were abstinent for 1 week preoperatively (n = 1519, OR = 1.229, 95% CI = 0.482-3.134, P = .666) or for 4 weeks preoperatively (n = 1576, OR = 1.902, 95% CI = 0.383-2.119, P = .812). CONCLUSION: Since smoking decreases the alveolar oxygen pressure and subcutaneous wound tissue oxygen, and nicotine causes vasoconstriction, smokers are more likely to experience flap loss, hematoma, or fat necrosis than non-smokers. Preoperative and post-operative abstinence period of at least 1 week is necessary for smokers who undergo flap operations.

OBJECTIF: La présente étude visait à comparer les complications des opérations par lambeau chez les non-fumeurs et les fumeurs et à déterminer l'effet d'une période d'abstinence du tabagisme avant et après l'opération par lambeau sur l'incidence de complications. MÉTHODOLOGIE: Dans PubMed et Scopus, les chercheurs ont utilisé les termes smoking ET flap survival et extrait 113 articles et 65 articles, respectivement. Après avoir exclu six articles dédoublés, ils ont examiné 172 titres et ont exclu 45 résumés. Ils ont révisé 20 articles complets et analysé 15 articles. RÉSULTATS: Les complications postopératoires comme la nécrose du lambeau (P < 0,001), l'hématome (P < .001) et la nécrose graisseuse (P = 0,003) étaient considérablement plus fréquentes chez les fumeurs que chez les non-fumeurs. Le taux de perte du lambeau était significativement plus élevé chez les fumeurs qui s'étaient abstenus de fumer 24 heures après l'opération que chez les non-fumeurs (n = 1 464, rapport de cotes [RC] = 4,885, intervalle de confiance [IC] à 95 % = 2,071 à 11,524, P < 0,001). Le taux de perte du lambeau était considérablement plus faible chez les fumeurs abstinents pendant une semaine après l'opération que chez ceux qui l'avaient été seulement 24 heures (n = 131, RC = 0,252, IC à 95 % = 0,074 à 0,851, P = 0,027). Les chercheurs n'ont constaté aucune différence significative de perte du lambeau entre les non-fumeurs et les fumeurs qui étaient abstinents une semaine avant l'opération (n = 1 519, RC = 1,229, IC 95 % = 0,482 à 3,134, P = 0,666) ou quatre semaines avant l'opération (n = 1 576, RC = 1,902, IC 95 % = 0,383 à 2,119, P = 0,812). CONCLUSION: Puisque le tabagisme réduit la pression de l'oxygène dans les alvéoles et dans les tissus mous des lésions sous-cutanées et que la nicotine est responsable d'une vasoconstriction, les fumeurs sont plus susceptibles que les non-fumeurs de présenter une perte du lambeau, un hématome ou une nécrose graisseuse. Chez les fumeurs, une période d'abstinence d'au moins une semaine s'impose avant et après les opérations par lambeau.