Assessment of anti-PD-(L)1 for patients with coexisting malignant tumor and tuberculosis classified by active, latent, and obsolete stage.

BACKGROUND: It is not a rare clinical scenario to have patients presenting with coexisting malignant tumor and tuberculosis. Whether it is feasible to conduct programmed death-(ligand) 1 [PD-(L)1] inhibitors to these patients, especially those with active tuberculosis treated with concurrent anti-tuberculosis, is still unknown. METHODS: This study enrolled patients with coexisting malignancy and tuberculosis and treated with anti-PD-(L)1 from Jan 2018 to July 2021 in 2 institutions. The progression-free survival (PFS), objective response rate (ORR), and safety of anti-PD-(L)1 therapy, as well as response to anti-tuberculosis treatment, were evaluated. RESULTS: A total of 98 patients were screened from this cohort study, with 45 (45.9%), 21 (21.4%), and 32 (32.7%) patients diagnosed with active, latent, and obsolete tuberculosis, respectively. The overall ORR was 36.0% for anti-PD-(L)1 therapy, with 34.2%, 35.5%, and 41.2% for each subgroup. Median PFS was 8.0 vs 6.0 vs 6.0 months (P=0.685) for each subgroup at the time of this analysis. For patients with active tuberculosis treated with concurrent anti-tuberculosis, median duration of anti-tuberculosis therapy was 10.0 (95% CI, 8.01-11.99) months. There were 83.3% (20/24) and 93.3% (42/45) patients showing sputum conversion and radiographic response, respectively, after anti-tuberculosis therapy, and two patients experienced tuberculosis relapse. Notably, none of the patients in latent and only one patient in obsolete subgroups showed tuberculosis induction or relapse after anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 33 patients (73.3%) when treated with concurrent anti-PD-(L)1 and anti-tuberculosis. Grade 3 or higher TRAEs were hematotoxicity (n = 5, 11.1%), and one patient suffered grade 3 pneumonitis leading to the discontinuation of immunotherapy. CONCLUSIONS: This study demonstrated that patients with coexisting malignant tumor and tuberculosis benefited equally from anti-PD-(L)1 therapy, and anti-tuberculosis response was unimpaired for those with active tuberculosis. Notably, the combination of anti-PD-(L)1 and anti-tuberculosis therapy was well-tolerated without significant unexpected toxic effects.

Efficacy and safety of concurrent anti-tuberculosis treatment and chemotherapy in lung cancer patients with co-existent tuberculosis.

BACKGROUND: This retrospective study evaluated the safety and efficacy of concurrent anti-tuberculosis (TB) and chemotherapy treatment in patients with advanced lung cancer and active TB. METHODS: We retrospectively analyzed patients who were first diagnosed with advanced lung cancer and received first-line chemotherapy in Guangzhou Chest Hospital from 2015 to 2017. Patients were categorized into two groups (2:1): lung cancer patients without active TB (Group A), and lung cancer patients with active TB (Group B). Primary endpoints included adverse events (AEs), objective response rate (ORR), time to treatment failure, and overall survival (OS). RESULTS: A total of 99 patients were eligible (Group A, n=66; Group B, n=33). Grade ≥3 treatment-related AEs, primarily hematologic toxicity, occurred in 39.4% and 51.5% of patients in Groups A and B, respectively. The hypohepatia in both groups was generally at grade 1 or 2, with similar incidences (26% and 27%, respectively). After two cycles of chemotherapy, the ORR was 42.4% and 33.3% in Group A and B, respectively (P=0.383). The median time to treatment failure (TTF) was 7.0 and 5.6 months for Groups A and B, respectively (P=0.175). The median OS was 17.0 and 14.0 months for Groups A and B, respectively (P=0.312). After 3 months of anti-TB treatment, all patients achieved sputum acid-fast bacilli (AFB) smear conversion and absorption on imaging, and the end of follow-up observed no recurrence. CONCLUSIONS: Concurrent anti-TB and chemotherapy treatment did not increase hematological toxicity or hypohepatia in lung cancer patients with pulmonary TB.

Comparison Between Endovascular and Open Surgery for the Treatment of Peripheral Artery Diseases: A Meta-Analysis.

The purpose of the study is to compare the efficacy and safety between endovascular surgery and open surgery for the treatment of peripheral arterial disease (PAD). Studies were recruited from EMBASE, PubMed, Cochrane Library, and reviewing reference lists of related studies between June 2017 and December 31, 2018. Data of functional outcomes were extracted in this meta-analysis. Odds ratio or standardized mean differences with its 95% confidence interval (95% CI) were used. Pooled data proved to be absent of heterogeneity were tested by a fixed-effects model; otherwise, we used a random-effects model. All analyses were managed with RevMan 5.3 software (Cochrane Collaboration, London, UK). Twenty-seven trials (7 randomized controlled trials and 20 retrospective trials) involving a total of 17,536 participants were included in our meta-analysis. Data showed that endovascular surgery was accompanied with lower complication rate (426/4,496 [9.48%] vs. 551/4,051 [13.60%]; 95% CI, 0.53 [0.34, 0.82]; I2 = 83%; P = 0.004) and shorter hospital stay (95% CI, -4.01 [-4.99, -3.02]; I2 = 76%; P < 0.00001) than open surgery. Higher amputation (204/1,633 [12.49%] vs. 228/1,247 [18.28%]; 95% CI, 0.72 [0.59, 0.89]; I2 = 12%; P = 0.002) and mortality during follow-up (490/4,514 [10.86%] vs. 341/4,520 [7.54%]; 95% CI, 0.73 [0.61, 0.86]; I2 = 0%; P < 0.05) were found in open surgery group. No evidence showed the rate of technical success, survival, or limb salvage reduced in endovascular surgery. In conclusion, our results showed that endovascular surgery is a promising technique for the treatment of PAD. Our data showed that endovascular surgery has less complication, shorter hospital stay, lower amputation, and mortality rate when compared with open surgery, although no significant difference was observed in survival rate, surgery success, and limb salvage.

Tumor Mutational Burden and Genomic Alterations in Chinese Small Cell Lung Cancer Measured by Whole-Exome Sequencing.

PURPOSE: Studies on genetic alterations of the heterogenous small cell lung cancer (SCLC) are rare. We carried out the present study to clarify the genomic alterations and TMB levels of Chinese SCLC patients by whole-exome sequencing. MATERIALS AND METHODS: Whole-exome sequencing by next-generation sequencing technique was implemented on twenty SCLC samples. Significant somatic mutations and copy number variations were screened, followed by comparison with the data extracted from COSMIC. Besides, altered signaling pathways were examined in order to figure out actionable targets. RESULTS: A total of 8,062 nonsynonymous mutations were defined. The number of mutations for each case ranged from 98 to 864. As for base substitutions, a total of 15,817 substitutions were detected with C > A conversion which was correlated to smoking occupying 25.57%. The TMB values ranged from 2.51/Mb to 22.1/Mb with a median value of 9.95/Mb. RB1 was the most frequently mutated gene altered in 18 (90%) cases, followed by TP53 altered in 17 (85%) cases. Other commonly changed genes were PTEN, and RBL1, with frequencies of 55% and 50%, respectively. SOX2 significantly amplified in 6 (30%) cases and MYCN amplified in 1 (5%) patient. Notch signaling pathway and PI3K/AKT/mTOR signaling pathway were universally and significantly changed. Major genomic alterations were in consistency with data from COSMIC, but frequencies of less common mutations were different. CONCLUSION: TP53 and RB1 inactivations were universally detected in SCLC. The Notch and PI3K/AKT/mTOR signaling pathways were both significantly altered, implying potential actionable targets.

[Analysis of ESAT-6-specific multifunctional CD4+; T cells in pleural fluid from patients with tuberculous pleurisy].

AIM: To evaluate cytokine production by CD4(+); T cells and frequency of multifunctional CD4(+); T cells after stimulation with ESAT-6 peptide pool. To understand the role of ESAT-6 specific CD4(+); T cells in the control of local TB infection. METHODS: PFCs were isolated from patients with tuberculous pleurisy, and assessed by flow cytometry for cytokine production, subpopulation, frequency and function of multifunctional CD4(+);T cells after stimulation with ESAT-6 peptide pool. RESULTS: Following stimulation with BCG, ESAT-6 peptide pool and recombinant ESAT-6 protein, CD4(+); but not CD8(+); T cells expressed IFN-γ, IL-2 and TNF-α. Distinct from BCG, ESAT-6 peptide pool and recombinant ESAT-6 protein induced similar frequencies of IFN-γ, IL-2 and TNF-α. High frequency of multifunctional CD4(+);T cells was observed. Analysis of mean fluorescence intensity (MFI) indicated that triple positive cells produced most amounts of cytokines on single cell level compared with double positive and single positive cells. CONCLUSION: ESAT-6 peptide pool predominantly induced Th1 cytokine production by CD4(+);T cells in PFCs. Multifunctional CD4(+); T cells were observed and secreted most amounts of cytokines on single cell level, suggesting that these cells probably played essential role in local TB infection.

[The clinical significance of changes in CD4+ T cell counts by peripheral blood from patients with pulmonary tuberculosis after antitubercular treatment].

AIM: To explore the clinical significance of changes in CD4+ T cell counts by peripheral blood from patients with pulmonary tuberculosis after antitubercular treatment. METHODS: CD4+ T cell counts in the peripheral blood of 62 pulmonary TB patients were counted by flow cytometry from groups auording to the radiologic extent of disease, and compared with those obtained from 30 controls. RESULTS: (1) The baseline levels of CD4+ T cell counts (439.21+/-210.56)/mm3 in pulmonary tuberculosis group before antituberculosis therapy were significantly lower than those (748.47+/-261.85)/mm3 in the control group (P<0.01). (2) The baseline levels of CD4+ T cell counts (399.83+/-194.17)/mm3 before antituberculosis therapy in diffuse group were significantly lower than those (521.90+/-224.40)/mm3 in limited group (P<0.05). (3) After two months of antituberculosis therapy, the levels of CD4+ T cell counts in the improved group increased from (480.75+/-228.49)/mm3 to (616.75+/-280.57)/mm3, and the values were not significantly different from those in controls (P>0.05). Whereas, the levels of CD4+ T cell counts in the stable group increased from (412.97+/-197.00)/mm3 to (447.55+/-204.60)/mm3, which were still significantly lower than those in the control group (P<0.01). CONCLUSION: These results suggested that peripheral CD4+ lymphopenia was demonstrated in patients with pulmonary tuberculosis, and such lymphopenia was reversible partly with antitubercular treatment. The numbers of peripheral CD4+ T cell counts were related to the severity of the disease, the more severe of the disease was, the less numbers of the CD4+ T cell counts were.