Lung Cancer Treatment Outcomes Research Articles

MicroRNA-130a-3p regulates osimertinib resistance by targeting runt-related transcription factor 3 in lung adenocarcinoma

Overcoming resistance to epidermal growth factor receptor tyrosine kinase inhibitors, including osimertinib, is urgent to improve lung cancer treatment outcomes. Extracellular vesicle (EV)-derived microRNAs (EV-miRNAs) play important roles in drug resistance and serve as promising biomarkers. In this study, we aimed to identify EV-miRNAs associated with osimertinib resistance and investigate their clinical relevance. The release of excess EVs was confirmed in the osimertinib-resistant lung adenocarcinoma cell line PC9OR. The exposure of PC9OR-derived EVs and EV-miRNAs to PC9 cells increased cell viability after osimertinib treatment. Microarray analysis revealed that miR-130a-3p was upregulated in EVs derived from PC9OR cells and another osimertinib-resistant cell line (H1975OR). Transfection with miR-130a-3p attenuated osimertinib-induced cytotoxicity and apoptosis in both PC9 and H1975 cells, whereas osimertinib resistance in PC9OR cells was reversed after miR-130a-3p inhibition. Bioinformatics analysis revealed that runt-related transcription factor 3 is a target gene of miR-130a-3p, and it induced osimertinib resistance in PC9 cells. Patients with lower baseline serum miR-130a-3p concentrations had longer progression-free survival. miR-130a-3p is a potential therapeutic target and a predictive biomarker of osimertinib resistance in adenocarcinomas.

Recent developments in the field of radiotherapy for the management of lung cancer.

Lung cancer has a poor prognosis, and further improvements in outcomes are needed. Radiotherapy plays an important role in the treatment of unresectable lung cancer, and there have been recent developments in the field of radiotherapy for the management of lung cancer. However, to date, there have been few reviews on the improvement in treatment outcomes associated with high precision radiotherapy for lung cancer. Thus, this review aimed to summarize the recent developments in radiotherapy techniques and indicate the future directions in the use of radiotherapy for lung cancer. Stereotactic body radiotherapy (SBRT) for unresectable stage I lung cancer has been reported to improve local control rates without severe adverse events, such as radiation pneumonitis. For locally advanced lung cancer, a combination of chemoradiotherapy and adjuvant immune checkpoint inhibitors dramatically improves treatment outcomes, and intensity-modulated radiotherapy (IMRT) enables safer radiation therapy with less frequent pneumonitis. Particle beam therapy, such as carbon-ion radiotherapy and proton beam therapy, has been administered as advanced medical care for patients with lung cancer. Since 2024, it has been covered under insurance for early stage lung cancer with tumors ≤ 5cm in size in Japan. In addition to chemotherapy, local ablative radiotherapy improves treatment outcomes in patients with oligometastatic stage IV lung cancer. A particular problem with radiotherapy for lung cancer is that the target location changes with respiratory motion, and various physical methods have been used to control respiratory motion. Recently, coronavirus disease has had a major impact on lung cancer treatment, and cancer treatment during situations, such as the coronavirus pandemic, must be performed carefully. To improve treatment outcomes for lung cancer, it is necessary to fully utilize evolving radiotherapy modalities, and the role of radiotherapy in lung cancer treatment is expected to increase.

Long-term Outcomes of Salvage Surgery Versus Induction Therapy Followed by Surgical Resection for Advanced NSCLC: A Propensity Score-matched Analysis.

The outcomes of lung cancer treatment have improved over time. However, in contrast to other treatments, the clinical outcomes of salvage surgery are seldom reported because the follow-up periods after salvage surgery are short. We conducted a comprehensive study involving consecutive patients who underwent salvage surgery at two different institutions. Our analysis encompassed the exploration of clinicopathological features, perioperative variables, and surgical outcomes. Additionally, we employed propensity score matching to compare the long-term survival of patients with non-small cell lung cancer (NSCLC) who underwent salvage surgery with those who received induction chemoradiotherapy prior to surgery. Twenty-five patients underwent salvage procedures, while 113 patients received induction chemotherapy followed by surgery during the same study period. When assessing the overall survival (OS) from the registration date to the initial treatment date, the five-year OS rates were 73.8% in the induction group and 70.5% in the salvage surgery group (p=0.674). No significant differences were identified between the two groups in a cohort of 48 patients with NSCLC who were matched using propensity scores. In patients who underwent salvage surgery, reasonable long-term survival was achieved with outcomes comparable to those of induction chemotherapy followed by surgical resection.

Inhalable explosive nanosensor for real-time visual monitoring of therapeutic effects of lung cancer

Lung cancer, as one of the major diseases that endanger human health, has a very high fatality rate. Consequently, effective evaluation of clinical treatment outcomes for lung cancer is crucial for the formulation of subsequent treatment plans for patients. In this work, we utilized amorphous calcium carbonate nanoparticles (CaCO3 NPs) as sources of calcium ions (Ca2+) to develop CPs (CaCO3@PDA) core–shell nanoprobes. Concurrently, we functionalized the surface of gold nanoparticles with Cy5.5-peptide, AS1411, and (4-aminosulfonylphenyl) boronic acid (4-APBA) to produce APAAs (Au NPs@pep-AS1411-(4-APBA)), which were further assembled with CPs using PEG to construct an innovative explosive nanosensor, CPAs (CaCO3@PDA-APAAs). The CPs component of the nanosensor could cause the release of a substantial amount of Ca2+ in response to the tumor microenvironment (TME), which in turn induced cellular Ca2+ overload and subsequent apoptosis. This event triggers caspase-3 activation, causing the cleavage of a specific peptide sequence (DEVD), resulting in the fluorescence signal being reinstated. Additionally, the 4-APBA moiety on the probe interacted with H2O2 resulting in alterations in surface-enhanced Raman spectroscopy (SERS) signals, which aided in the detection of reactive oxygen species (ROS) during the physiological processes. By utilizing atomization, the nanoprobes were strategically deposited in the affected lung regions to enhance the fluorescence imaging capabilities and effectively mirror the therapeutic outcomes. Overall, the CPAs explosive nanosensor has a potential in advancing the non-invasive visual monitoring of lung cancer prognosis and can be a valuable tool in ongoing efforts to improve the management of this challenging disease.

The Role of AKR1B10 in Lung Cancer Malignancy Induced by Sublethal Doses of Chemotherapeutic Drugs.

Chemotherapy remains a cornerstone in lung cancer treatment, yet emerging evidence suggests that sublethal low doses may inadvertently enhance the malignancy. This study investigates the paradoxical effects of sublethal low-dose chemotherapy on non-small-cell lung cancer (NSCLC) cells, emphasizing the role of Aldo-keto reductase family 1 member B10 (AKR1B10). We found that sublethal doses of chemotherapy unexpectedly increased cancer cell migration approximately 2-fold and invasion approximately threefold, potentially promoting metastasis. Our analysis revealed a significant upregulation of AKR1B10 in response to taxol and doxorubicin treatment, correlating with poor survival rates in lung cancer patients. Furthermore, silencing AKR1B10 resulted in a 1-2-fold reduction in cell proliferation and a 2-3-fold reduction in colony formation and migration while increasing chemotherapy sensitivity. In contrast, the overexpression of AKR1B10 stimulated growth rate by approximately 2-fold via ERK pathway activation, underscoring its potential as a target for therapeutic intervention. The reversal of these effects upon the application of an ERK-specific inhibitor further validates the significance of the ERK pathway in AKR1B10-mediated chemoresistance. In conclusion, our findings significantly contribute to the understanding of chemotherapy-induced adaptations in lung cancer cells. The elevated AKR1B10 expression following sublethal chemotherapy presents a novel molecular mechanism contributing to the development of chemoresistance. It highlights the need for strategic approaches in chemotherapy administration to circumvent the inadvertent enhancement of cancer aggressiveness. This study positions AKR1B10 as a potential therapeutic target, offering a new avenue to improve lung cancer treatment outcomes by mitigating the adverse effects of sublethal chemotherapy.

Overexpression of TNFSF11 reduces GPX4 levels and increases sensitivity to ferroptosis inducers in lung adenocarcinoma

BackgroundLung adenocarcinoma (LUAD), the most common and lethal subtype of lung cancer, continues to be a major health concern worldwide. Despite advances in targeted and immune therapies, only a minority of patients derive substantial benefits. As a result, the urgent need for novel therapeutic strategies to improve lung cancer treatment outcomes remains undiminished.MethodsIn our study, we employed the TIMER database to scrutinize TNFSF11 expression across various cancer types. We further examined the differential expression of TNFSF11 in normal and tumor tissues utilizing the TCGA-LUAD dataset and tissue microarray, and probed the associations between TNFSF11 expression and clinicopathological parameters within the TCGA-LUAD dataset. We used the GSE31210 dataset for external validation. To identify genes strongly linked to TNFSF11, we engaged LinkedOmics and conducted a KEGG pathway enrichment analysis using the WEB-based Gene SeT AnaLysis Toolkit. Moreover, we investigated the function of TNFSF11 through gene knockdown or overexpression approaches and explore its function in tumor cells. The therapeutic impact of ferroptosis inducers in tumors overexpressing TNFSF11 were also investigated through in vivo and in vitro experiments. Through these extensive analyses, we shed light on the potential role of TNFSF11 in lung adenocarcinoma, underscoring potential therapeutic targets for this malignancy.ResultsThis research uncovers the overexpression of TNFSF11 in LUAD patients and its inverse correlation with peroxisome-related enzymes. By utilizing gene knockdown or overexpression assays, we found that TNFSF11 was negatively associated with GPX4. Furthermore, cells with TNFSF11 overexpression were relatively more sensitive to the ferroptosis inducers.ConclusionsOur research has provided valuable insights into the role of TNFSF11, revealing its negative regulation of GPX4, which could be influential in crafting therapeutic strategies. These findings set the stage for further exploration into the mechanisms underpinning the relationship between TNFSF11 and GPX4, potentially opening up new avenues for precision medicine in the treatment of LUAD.

Oncolytic viruses in lung cancer treatment: a review article.

Lung cancer has a high morbidity rate worldwide due to its resistance to therapy. So new treatment options are needed to improve the outcomes of lung cancer treatment. This study aimed to evaluate the effectiveness of oncolytic viruses (OVs) as a new type of cancer treatment. In this study, 158 articles from PubMed and Scopus from 1994 to 2022 were reviewed on the effectiveness of OVs in the treatment of lung cancer. The oncolytic properties of eight categories of OVs and their interactions with treatment options were investigated. OVs can be applied as a promising immunotherapy option, as they are reproduced selectively in different types of cancer cells, cause tumor cell lysis and trigger efficient immune responses.

NAD (P)H Quinone Dehydrogenase 1-Targeting Triptolide Analogue Causes Tumor Regression and Sensitizes Cisplatin-Resistant Lung Cancer to Chemotherapy.

Cisplatin (DDP) is a first-line chemotherapeutic drug against lung cancer. Nonetheless, the effectiveness of this drug is hampered by drug resistance. Overcoming drug resistance is crucial for improving the outcomes of lung cancer treatment. Here, we reported the effect of CX-23, an activated triptolide analogue that targets NAD (P)H quinone dehydrogenase 1 (NQO1), on DDP-resistant lung cancer and sensitizes DDP-resistant lung cancer to chemotherapy. Our findings unveiled the antiproliferative activity of CX-23 against both A549- and DDP-resistant A549 (A549/DDP) cells while enhancing the chemosensitivity of these cells to DDP. Notably, CX-23 demonstrated no toxicity toward normal lung cells. Further investigations revealed that CX-23 exerts its effects by blocking AKT phosphorylation, leading to reduced expression of Mcl-1 and Bcl-2, and upregulating cleaved-caspase-3 levels, ultimately inducing apoptosis in cancer cells. CX-23 can be rapidly transformed in both A549 and A549/DDP cell lysates while remaining stable in mouse plasma and normal lung tissues. Pharmacokinetic analysis showed that CX-23 can distribute to lung tissues. Moreover, in vivo studies showed that CX-23 can prevent DDP-resistant lung cancer progression without causing any toxicity in the liver, kidneys, or lungs after 6 weeks of treatment. The combination of CX-23 and DDP not only significantly inhibited tumor progression compared to DDP alone but also attenuated DDP-induced kidney toxicity. These findings suggest that CX-23 alone or in combination with DDP may provide an alternative therapeutic option for DDP-resistant lung cancer.

Fabricating niosomal-PEG nanoparticles co-loaded with metformin and silibinin for effective treatment of human lung cancer cells.

Despite current therapies, lung cancer remains a global issue and requires the creation of novel treatment methods. Recent research has shown that biguanides such as metformin (MET) and silibinin (SIL) have a potential anticancer effect. As a consequence, the effectiveness of MET and SIL in combination against lung cancer cells was investigated in this study to develop an effective and novel treatment method. Niosomal nanoparticles were synthesized via the thin-film hydration method, and field emission scanning electron microscopy (FE-SEM), Fourier transform infrared (FTIR), atomic force microscopy (AFM), and dynamic light scattering (DLS) techniques were used to evaluate their physico-chemical characteristics. The cytotoxic effects of free and drug-loaded nanoparticles (NPs), as well as their combination, on A549 cells were assessed using the MTT assay. An apoptosis test was used while under the influence of medication to identify the molecular mechanisms behind programmed cell death. With the use of a cell cycle test, it was determined whether pharmaceutical effects caused the cell cycle to stop progressing. Additionally, the qRT-PCR technique was used to evaluate the levels of hTERT, BAX, and BCL-2 gene expression after 48-h medication treatment. In the cytotoxicity assay, the growth of A549 lung cancer cells was inhibited by both MET and SIL. Compared to the individual therapies, the combination of MET and SIL dramatically and synergistically decreased the IC50 values of MET and SIL in lung cancer cells. Furthermore, the combination of MET and SIL produced lower IC50 values and a better anti-proliferative effect on A549 lung cancer cells. Real-time PCR results showed that the expression levels of hTERT and BCL-2 were significantly reduced in lung cancer cell lines treated with MET and SIL compared to single treatments (p< 0.001). It is anticipated that the use of nano-niosomal-formed MET and SIL would improve lung cancer treatment outcomes and improve the therapeutic efficiency of lung cancer cells.

Mechanistic modeling of anti-microRNA-155 therapy combinations in lung cancer.

To improve treatment outcomes in non-small cell lung cancer (NSCLC), it is crucial to identify treatment strategies with the potential to exhibit drug synergism. This can lower the required effective dose, reducing exposure to drugs and associated toxicities, while improving treatment efficacy. In previous studies, drugs targeting the microRNA-155 or PD-L1 have been promising in restraining NSCLC tumor growth. We have developed a mathematical model that simulates the in vivo pharmacokinetics and pharmacodynamics of the novel nanoparticle-delivered anti-microRNA-155 for potential use with standard-of-care drug atezolizumab for NSCLC. Through modeling and simulation, we identified possible drug synergism between the two drugs that holds promise to improve tumor response at reduced drug exposure.Clinical Relevance-Identifying the possibility of drug synergism for an anti-microRNA-155 based nanotherapeutic with standard-of-care immunotherapy to improve lung cancer treatment outcomes.

Potential Applications of Nanoparticles in Improving the Outcome of Lung Cancer Treatment.

Lung cancer is managed using conventional therapies, including chemotherapy, radiation therapy, or a combination of both. Each of these therapies has its own limitations, such as the indiscriminate killing of normal as well as cancer cells, the solubility of the chemotherapeutic drugs, rapid clearance of the drugs from circulation before reaching the tumor site, the resistance of cancer cells to radiation, and over-sensitization of normal cells to radiation. Other treatment modalities include gene therapy, immunological checkpoint inhibitors, drug repurposing, and in situ cryo-immune engineering (ICIE) strategy. Nanotechnology has come to the rescue to overcome many shortfalls of conventional therapies. Some of the nano-formulated chemotherapeutic drugs, as well as nanoparticles and nanostructures with surface modifications, have been used for effective cancer cell killing and radio sensitization, respectively. Nano-enabled drug delivery systems act as cargo to deliver the sensitizer molecules specifically to the tumor cells, thereby enabling the radiation therapy to be more effective. In this review, we have discussed the different conventional chemotherapies and radiation therapies used for inhibiting lung cancer. We have also discussed the improvement in chemotherapy and radiation sensitization using nanoparticles.

The impact of COVID-19 on the survival outcome of lung cancer at a Canadian academic centre: A real-world data analysis.

e21200 Background: The Covid-19 pandemic directly affected the screening, diagnosis, and treatment of lung cancer patients. Our group recently reported that the rate of new lung cancer diagnoses declined during the first year and significantly increased during the second of COVID-19 pandemic. The effect of COVID-19 on lung cancer treatment outcomes in literature is still limited and mostly reported either as predictive survival using prioritization and modeling techniques. In this study, we aimed to quantify the effect of COVID-19 on lung cancer survival using real world data collected at the Jewish General Hospital, Montreal. Methods: This is a retrospective chart review study including patients diagnosed with lung cancer between March 2019 and March 2022. We compared 3 cohorts: Cohort1: 2019 (pre-COVID) Cohort2: 2020 (1st year of COVID) Cohort3: 2021 (2nd year of COVID). Results: A total of 417 patients were diagnosed and treated with lung cancer at our centre throughout the three-year study: 130 in 2019, 103 in 2020 and 184 in 2021. Although the proportion of advanced/metastatic stage lung cancer remained the same for the three cohorts, there was a significant increase in the late-stage presentation during the pandemic. The proportion of M1c (multiple extrathoracic sites) cases in Cohorts 2 and 3 was 57% and 51% respectively compared to 31% in cohort 1 (p &lt; 0.05). Median survival for early and locally advanced stages of lung cancer was similar in the 3 cohorts. However, the subgroup of patients diagnosed in the advanced/metastatic stage had a significantly increased risk of death during the pandemic (cohorts 2 and 3). The 6-month mortality rate was 53% in 2021 compared to 47% in 2020 and 29% in 2019 (p = 0.004). The median survival in this subgroup of patients decreased significantly from 13 months in 2019 to 6 months in 2020 and 5 months in 2021 (Table 1). Conclusions: The present study represents the impacts of the COVID-19 on lung cancer survival outcome. The COVID-19 pandemic potentially caused the significant shift to M1c stage and contributed to an increase 6 month mortality rate and poorer overall survival in the advanced/metastatic lung cancer patients diagnosed and treated during the pandemic.[Table: see text]

MicroRNA, mRNA, and Proteomics Biomarkers and Therapeutic Targets for Improving Lung Cancer Treatment Outcomes.

The majority of lung cancer patients are diagnosed with metastatic disease. This study identified a set of 73 microRNAs (miRNAs) that classified lung cancer tumors from normal lung tissues with an overall accuracy of 96.3% in the training patient cohort (n = 109) and 91.7% in unsupervised classification and 92.3% in supervised classification in the validation set (n = 375). Based on association with patient survival (n = 1016), 10 miRNAs were identified as potential tumor suppressors (hsa-miR-144, hsa-miR-195, hsa-miR-223, hsa-miR-30a, hsa-miR-30b, hsa-miR-30d, hsa-miR-335, hsa-miR-363, hsa-miR-451, and hsa-miR-99a), and 4 were identified as potential oncogenes (hsa-miR-21, hsa-miR-31, hsa-miR-411, and hsa-miR-494) in lung cancer. Experimentally confirmed target genes were identified for the 73 diagnostic miRNAs, from which proliferation genes were selected from CRISPR-Cas9/RNA interference (RNAi) screening assays. Pansensitive and panresistant genes to 21 NCCN-recommended drugs with concordant mRNA and protein expression were identified. DGKE and WDR47 were found with significant associations with responses to both systemic therapies and radiotherapy in lung cancer. Based on our identified miRNA-regulated molecular machinery, an inhibitor of PDK1/Akt BX-912, an anthracycline antibiotic daunorubicin, and a multi-targeted protein kinase inhibitor midostaurin were discovered as potential repositioning drugs for treating lung cancer. These findings have implications for improving lung cancer diagnosis, optimizing treatment selection, and discovering new drug options for better patient outcomes.

Abstract 264: Framework to determine fusion junction of novel RNA fusions and their actionability for personalized therapy of lung cancer patients

Abstract Background: Current therapies including chemotherapy, radiotherapy, and targeted therapies have not worked well for treating lung cancer as is evident by the high lung cancer-related mortality rate. This is because we continue to treat all lung cancers as a homogenous disease. Therefore, personalized therapies based on individual molecular characteristics of patient tumors are needed to improve lung cancer treatment outcomes. Objective: The objective of the current project is to identify novel actionable RNA fusions that can be targeted for the personalized treatment of lung cancer. Fusions, including the ones that are created by joining at the RNA level, can form during cancer development and thus present an attractive way of personalized cancer treatment. Methodology: A list of RNA fusion candidates was processed through a multistep pipeline framework to map the fusion junction of these novel fusions and evaluate their actionability. We had previously obtained this list of RNA fusions by mining the RNA sequencing data from lung cancer samples. The workflow of the project included the following steps: 1) a literature search to assess the oncogenic role of individual gene partners, 2) Blat to map the fusion junction 3) cBioPortal/Survival analysis to predict the association of individual gene partners with lung cancer patient survival and prognosis, 4) cBioPortal/Co-Expression analysis to study if the gene partners are expressed together or have common gene partners and lastly, 5) Open Reading Frame (ORF) Finder to identify if the fusion is predicted to be translated and makes a unique product. Results: RNA fusions such as TMPRSS13-TMPRSS13, SUPT6H-ESR1, PTPRK-RSPO3, and KIF5B-RET were investigated and fusion junctions were successfully determined. Gene partners from multiple fusion pairs (e.g., SUPT6H-ESR1 and KIF5B-RET) were found to have an oncogenic role in lung cancer. Mutations in KIF5B and RET genes were found to associate with poor survival in the TCGA dataset suggesting that the novel RNA fusions may also play an oncogenic role in lung cancer. Lastly, several of these RNA fusions generated unique ORFs suggesting that these fusions are predicted to be translated and these novel proteins can be selectively targeted sparing the normal cells that don’t harbor these mutants. Future directions: Next steps will involve preclinical testing of the driver role of these novel RNA fusions and testing of existing drugs such as RET inhibitors for their efficacy to treat lung cancer in tumors that harbor these novel RNA fusions. Citation Format: Prisha Verma, Sakuni Rankothgedera, Micah Castillo, Preethi Gunaratne. Framework to determine fusion junction of novel RNA fusions and their actionability for personalized therapy of lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 264.

Novel nutritional indicator as predictors among subtypes of lung cancer in diagnosis.

Lung cancer is a serious global health concern, and its subtypes are closely linked to lifestyle and dietary habits. Recent research has suggested that malnutrition, over-nutrition, electrolytes, and granulocytes have an effect on the development of cancer. This study investigated the impact of combining patient nutritional indicators, electrolytes, and granulocytes as comprehensive predictors for lung cancer treatment outcomes, and applied a machine learning algorithm to predict lung cancer. 6,336 blood samples were collected from lung cancer patients classified as lung squamous cell carcinoma (LUSC), lung adenocarcinoma (LUAD), and small cell lung cancer (SCLC). 2,191 healthy individuals were used as controls to compare the differences in nutritional indicators, electrolytes and granulocytes among different subtypes of lung cancer, respectively. Our results demonstrated significant differences between men and women in healthy people and NSCLC, but no significant difference between men and women in SCLC patients. The relationship between indicators is basically that the range of indicators for cancer patients is wider, including healthy population indicators. In the process of predicting lung cancer through nutritional indicators by machine learning, the AUC of the random forest model was as high as 93.5%, with a sensitivity of 75.9% and specificity of 96.5%. This study supports the feasibility and accuracy of nutritional indicators in predicting lung cancer through the random forest model. The successful implementation of this novel prediction method could guide clinicians in providing both effective diagnostics and treatment of lung cancers.

Clinicopathological profile and treatment outcomes of lung cancer: An ambispective study from south India

Clinicopathological profile and treatment outcomes of lung cancer: An ambispective study from south India

Cachexia index as a potential biomarker for cancer cachexia and a prognostic indicator in diffuse large B-cell lymphoma.

BackgroundCancer cachexia is known to adversely affect the clinical course in patients with malignant lymphoma. The cachexia index (CXI) is a potential biomarker of cancer cachexia, and its implications for the prognosis and treatment outcome of lung cancer and aggressive lymphoma has been assessed in previous studies.MethodsA total of 267 patients diagnosed with diffuse large B‐cell lymphoma who were treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R‐CHOP) immunochemotherapy were retrospectively reviewed. The CXI was calculated as the skeletal muscle index (SMI) × serum albumin/neutrophil–lymphocyte ratio (NLR). Although previous studies measured the SMI using the muscles of the L3 vertebral level, the present study used both the L3 vertebral muscles and the pectoralis muscles (PM) at the T4 vertebral level to measure the SMI. Depending on the type of muscles used, the CXI was termed the L3‐CXI or PM‐CXI. Using sex‐specific cutoff values for CXI, the patients were categorized as follows: (i) high‐CXI group (high L3‐CXI and high PM‐CXI), (ii) intermediate‐CXI group (high L3‐CXI and low PM‐CXI), and (iii) low‐CXI group (low L3‐CXI and low PM‐CXI).ResultsComplete responses to R‐CHOP were obtained in 145/173 (83.8%), 25/36 (69.4%), and 27/57 (47.4%) patients in the high‐CXI, intermediate‐CXI, and low‐CXI groups, respectively (P < 0.001). Treatment‐related anaemia (15.6%, 30.6%, and 26.3%, P = 0.038), thrombocytopenia (21.4%, 36.1%, and 43.9%, P < 0.001), febrile neutropenia (23.7%, 44.4%, and 36.8%, P = 0.022), and any nonhaematologic toxicity (31.2%, 44.4%, and 54.4%, P = 0.001) of Grade 3 or more were more common in the lower CXI groups than in the higher‐CXI groups. Early treatment discontinuation for reasons other than lymphoma progression also occurred more frequently in the low‐CXI group (24/57, 42.1%) compared with the intermediate‐CXI (5/36, 13.9%) and high‐CXI (18/173, 10.4%) groups (P < 0.001). Median overall survival in the high‐CXI, intermediate‐CXI, and low‐CXI groups was not reached, 50.6 months, and 14.5 months, respectively (p < 0.001). Multivariable analysis showed that low CXI was an independent negative prognostic factor for overall survival (hazard ratio 2.103, 95% confidence interval 1.278–3.460, P = 0.003).ConclusionsWe suggest that in patients with diffuse large B‐cell lymphoma, the CXI is a biomarker for cancer cachexia that can predict survival, treatment response, treatment‐related toxicity, and compliance with R‐CHOP. Patients were more clearly stratified by this new CXI category compared with the classifications described in previous studies.

Antimalarial Atovaquone May Improve Lung Cancer Treatment Outcomes

Antimalarial Atovaquone May Improve Lung Cancer Treatment Outcomes

NoduleNet: A Lung Nodule Classification Using Deep Learning

Background: Accurate detection and classification of lung nodules at an early stage can help physicians to improve the treatment outcomes of lung cancer. Several lung nodule classifications using deep learning have been proposed but they are lag of external validation to Thai patient data.&#x0D; Objective: To propose a deep learning model called NoduleNet for lung nodule classification and perform internal and external validation of the proposed model.&#x0D; Methods: Two datasets were performed; internal validation using LUNA16 (the public lung CT database), and external validation using ChestRama (37 chest CT scans retrospectively identified from the CT database of Ramathibodi Hospital between 2017 and 2019). The NoduleNet was built on top of pretrained architecture, VGG16, and VGG19 with customization.&#x0D; Results: The NoduleNet showed impressive results in nodule classification. The best model achieved accuracy of 0.95 (0.94 - 0.96), sensitivity of 0.84 (0.82 - 0.86), and specificity of 0.97 (0.97 - 0.98) for internal validation, where the external validation results was accuracy of 0.95 (0.87 - 1.00), sensitivity of 0.91 (0.82 - 1.00), and specificity of 1.00 (1.00 - 1.00). There were 3 misclassified samples in external validation which are all false-negative.&#x0D; Conclusions: The NoduleNet is able to generalize from non-Thai patient data to Thai patient data. It could be further improved by taking sequence of images into account, integrating with an automatic nodule detection algorithm, and adding more nodule types.

Worse outcomes after conversion of thoracoscopic lobectomy for lung cancer.

Conversion of thoracoscopic lobectomy for lung cancer to thoracotomy can adversely affect short-term outcomes, but the impact on long-term outcomes is unknown. This study aimed to identify the risk factors for conversion and to determine the influence of conversion on the outcomes of lung cancer treatment. This retrospective study included 1002 consecutive patients with lung cancer who underwent thoracoscopic lobectomy between 7 June 1999 and 17 July 2018. The groups of patients with and without conversion were compared in terms of possible risk factors and the short- and long-term outcomes. The survival of patients was analysed by the Kaplan-Meier method. Conversion was done in 105 patients (10.5%). On multivariable logistic regression analysis, the independent risk factors for conversion were pleural adhesions (P < 0.001) and mediastinal lymph node metastases (P < 0.001). Compared with the non-conversion group, the conversion group had longer chest drainage time (4 vs 3 days, P < 0.001) and hospital stay (8 vs 6 days, P < 0.001); more frequent complications (38.1% vs 27.1%, P = 0.018), including red blood cell transfusion (10.5% vs 2%, P < 0.001) and supraventricular arrhythmia (13.3% vs 7.5%, P = 0.037); and lower 5-year survival rate in patients with stage I lung cancer (70% vs 87%, P = 0.014). Conversion did not increase in-hospital mortality. Pleural adhesions and lymph node metastases increased the probability of conversion to thoracotomy. Conversion adversely affected the short-term outcomes of thoracoscopic lobectomy. Long-term outcomes of treatment of non-small-cell lung cancer could be worse in patients after conversion, but definitive conclusions cannot be made in this regard because of the absence of control of selection bias.