Therapy For Lung Cancer Patients Research Articles

Tumor promoting effect of PDLIM2 downregulation involves mitochondrial ROS, oncometabolite accumulations and HIF-1α activation

BackgroundCancer is characterized by dysregulated cellular metabolism. Thus, understanding the mechanisms underlying these metabolic alterations is important for developing targeted therapies. In this study, we investigated the pro-tumoral effect of PDZ and LIM domain 2 (PDLIM2) downregulation in lung cancer growth and its association with the accumulation of mitochondrial ROS, oncometabolites and the activation of hypoxia-inducible factor-1 (HIF-1) α in the process.MethodsDatabases and human cancer tissue samples were analyzed to investigate the roles of PDLIM2 and HIF-1α in cancer growth. DNA microarray and gene ontology enrichment analyses were performed to determine the cellular functions of PDLIM2. Seahorse assay, flow cytometric analysis, and confocal microscopic analysis were employed to study mitochondrial functions. Oncometabolites were analyzed using liquid chromatography–mass spectrometry (LC–MS). A Lewis lung carcinoma (LLC) mouse model was established to assess the in vivo function of PDLIM2 and HIF-1α.ResultsThe expression of PDLIM2 was downregulated in lung cancer, and this downregulation correlated with poor prognosis in patients. PDLIM2 highly regulated genes associated with mitochondrial functions. Mechanistically, PDLIM2 downregulation resulted in NF-κB activation, impaired expression of tricarboxylic acid (TCA) cycle genes particularly the succinate dehydrogenase (SDH) genes, and mitochondrial dysfunction. This disturbance contributed to the accumulation of succinate and other oncometabolites, as well as the buildup of mitochondrial reactive oxygen species (mtROS), leading to the activation of hypoxia-inducible factor 1α (HIF-1α). Furthermore, the expression of HIF-1α was increased in all stages of lung cancer. The expression of PDLIM2 and HIF-1α was reversely correlated in lung cancer patients. In the animal study, the orally administered HIF-1α inhibitor, PX-478, significantly reduces PDLIM2 knockdown-promoted tumor growth.ConclusionThese findings shed light on the complex action of PDLIM2 on mitochondria and HIF-1α activities in lung cancer, emphasizing the role of HIF-1α in the tumor-promoting effect of PDLIM2 downregulation. Additionally, they provide new insights into a strategy for precise targeted treatment by suggesting that HIF-1α inhibitors may serve as therapy for lung cancer patients with PDLIM2 downregulation.

Sevoflurane inhibits lung cancer development by promoting FUS1 transcription via downregulating IRF6.

Lung cancer is a major contributor to cancer deaths worldwide and is on the rise. Although surgical resection has been widely used as a standard of therapy for lung cancer patients, the relapse rate after surgery is high. It is still unclear whether there is a potential drug that can reduce the probability of post-surgical recurrence in lung cancer patients. We used five typical lung cancer cell lines as well as 41 lung cancer tissue samples and paracancer tissue samples to investigate the expression levels of IRF6 and FUS1. We also treated lung cancer cells (H322 and A549) with different concentrations of sevoflurane to study its influence on lung cancer cell tumorigenesis. Lentivirus-mediated gain-of-function studies of IRF6 and FUS1 were applied to validate the role of IRF6 and FUS1 in lung cancer. Next, we used short hairpin RNA-mediated loss of function of IRF6 and luciferase, ChIP assays to validate the regulatory role of IRF6 on FUS1. Our findings reported that IRF6 was up-regulated in lung cancer tissues, while FUS1 was down-regulated. Functional assays revealed that sevoflurane inhibits lung cancer development by downregulating IRF6 expression. Luciferase assay and ChIP-qPCR assay uncovered that IRF6 represses FUS1 transcriptional expression in lung cancer cells. We have shown that sevoflurane prevents lung cancer development by downregulating IRF6 to stimulate FUS1 transcription; indicating that sevoflurane can be used as the potential anesthetic drug in surgical resection to reduce post-operative tumor relapse in lung cancer patients.

Comparison of diagnostic performance between Oncomine Dx target test and AmoyDx panel for detecting actionable mutations in lung cancer

Companion diagnostic (CDx) tests play important roles in identifying oncogenic driver genes and tailoring effective molecularly targeted therapies for lung cancer patients. In Japan, the Oncomine Dx target test (ODxTT) and the AmoyDx pan lung cancer PCR panel (AmoyDx) are prominent CDx tests and only one of these tests is covered by the domestic insurance system. However, these CDx tests cover different target regions and apply different technologies (ODxTT is amplicon-based next-generation sequencing and AmoyDx is multiplex PCR-based assay), which may lead to missing of actionable mutations affecting patient prognosis. Here, we performed a direct comparison analysis of 1059 genetic alterations of eight driver genes from 131 samples and evaluated the concordance between two CDx tests for detecting actionable variants and fusions. When excluding the eight uncovered variants (ODxTT: two variants, AmoyDx: six variants), the overall percent agreement was 97.6% (1026/1051) with 89.0% of overall positive percent agreement (89/100) and 98.5% of overall negative percent agreement (937/951). Of the 25 discordant genetic alterations, two were undetected despite being covered in the AmoyDx (one EGFR variant and one ROS1 fusion). Furthermore, there were potential false positives in the ODxTT (nine MET exon 14 skippings) and in the AmoyDx (five variants, six ROS1 and three RET fusions). These potential false positives in the AmoyDx likely due to non-specific amplification, which was validated by the unique molecular barcoding sequencing. The ODxTT missed two uncovered EGFR rare variants, which was visually confirmed in the raw sequencing data. Our study provides insights into real-world performance of CDx tests for lung cancer and ensures reliability to advance precision medicine.

Balancing robustness and adaptation rate for proton therapy of lung cancer patients

IntroductionAn increase in plan robustness leads to a higher dose to organs-at-risk (OARs), and an increased chance of post-treatment toxicities. In contrast, more conformal plans lead to sparing of healthy surrounding tissue at the expense of a higher sensitivity to anatomical changes, requiring costly adaptations. In this study, we assess the trade-off and impact of treatment plan robustness on the adaptation rate. MethodTreatment planning was performed for 40 lung cancer patients, each having a planning 4DCT and up to eight weekly repeated 4DCTs (reCTs). For each patient, plans were made with three different levels of robustness based on setup uncertainty of 3, 6 and 9 mm. These plans were robustly re-evaluated on all reCTs to assess whether the clinical constraints were met. ResultsFor the 3, 6 and 9 mm robustness levels, adaptation rates of 87.5 %, 70.0 % and 57.5 %, respectively, were observed. A mean absolute normal tissue complication probability (NTCP) gain of 2.9 percentage points (pp) was calculated for pneumonitis grade ≥ 2 when transitioning from 9 mm plans to 3 mm plans, 7.6 pp for esophagitis grade ≥ 2, and 2.5 pp for mortality risk 2 years post-treatment. ConclusionThe lowered risk of post treatment toxicities at lower robustness levels is clinically relevant but comes at the expense of more treatment adaptations, particularly in cases where meeting our clinical goals is not compromised by having a dose that is more conformal to the target. The trade-off between workload and reduced NTCP needs to be individually assessed.

GPRC5A promotes paclitaxel resistance and glucose content in NSCLC.

Lung cancer is one of the most common and malignant cancers worldwide. Chemotherapy has been widely used in the clinical setting, and paclitaxel is the first-line therapy for lung cancer patients but paclitaxel resistance is the main problem. First, we successfully established paclitaxel-resistant lung cancer cells treated with elevated doses of paclitaxel for 3 months, as confirmed by the CCK-8 assay. Paclitaxel-resistant cancer cells increased glucose content. Second, Gtex, Oncomine, and gene expression omnibus database data mining identified GPRC5A, G protein-coupled receptor, as the most prominent differentially expressed gene in drug-resistant datasets including gemcitabine, paclitaxel, and gefitinib overlapped with the microarray data from cancer cell metabolism. Third, qPCR analysis and western blot technique showed that GPRC5A mRNA and protein levels were significantly enhanced in paclitaxel-resistant lung cancer cells. Fourth, functional analysis was conducted by siRNA-mediated transient knockdown of GPRC5A. Silencing GPRC5A significantly decreased paclitaxel resistance and glucose content. In the end, retinoic acid substantially upregulated GPRC5A proteins and promoted glucose content in two lung cancer cells. Kaplan-Meier plot also confirmed that lung cancer patients with high expression of GPRC5A had a relatively lower survival rate. Our study provided a potential drug target GPRC5A, which may benefit lung cancer patients with acquired paclitaxel resistance in the future and a theoretical basis for future preclinical trials.

Abstract 7528: Coordinated regulation of critical immune checkpoint proteins by the integrated stress response (ISR) pathway in lung cancer

Abstract Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Despite recent advances, high rates of recurrence highlight the need for novel treatment options. Groundbreaking discoveries in identifying and exploiting the PD-1/PD-L1 (Programmed Death 1/Programmed Death Ligand 1) immune checkpoint have resulted in the approval of monoclonal antibodies that disrupt this interaction as a first-line therapy for lung cancer patients. However, only ~20% of NSCLC patients benefit from checkpoint blockade. A critical question remains as to what mechanisms facilitate resistance to PD-1/PD-L1 therapy and whether other immune checkpoints or pathways can be pursued clinically in combination with this therapy. The integrated stress response (ISR) pathway represents an emerging therapeutic vulnerability. The ISR is a generalized response to maintain cellular homeostasis, and is known to be activated by hypoxia, heme deprivation, amino acid starvation, and oncogenic activation. We previously demonstrated that ISR activation potently induces PD-L1 in NSCLC and suppression of anti-tumor immunity (Suresh et al, Nature Cancer, 2020). We discovered that ISR pathway activation enhances PD-L1 translation through the bypass of inhibitory upstream open reading frames (uORFs) in the PD-L1 5' UTR and a mechanistic link to the translation initiation factor eIF5B. Our latest studies demonstrate that the immune checkpoint protein, CD155 (Cluster of Differentiation 155), is induced by ISR activation. We find that both PD-L1 and CD155 are induced by multiple arms of the ISR pathway, and CD155 harbors inhibitory uORFs in its 5' UTR. Importantly, we observed a significant correlation between PD-L1 and CD155 expression in a panel of primary human lung adenocarcinomas. We further demonstrated that ISR activation inhibits T cell function in vitro and promotes tumor growth in the CMT167 syngeneic mouse model. Analysis of immune cell infiltration using mass cytometry in this in vivo model is ongoing. Currently, we are determining the extent to which ISR inhibition suppresses tumorigenesis by promoting anti-tumor immunity and whether this may synergize with existing immune checkpoint therapies. Overall, these studies will set the stage for determining whether inhibition of the ISR pathway alone or in combination with immune checkpoint blockade will benefit lung cancer patients. Our studies may also lead to new therapeutic approaches to trigger anti-cancer immune responses and improve current strategies. Citation Format: Shayna Elizabeth Thomas-Jardin, Shruthy Suresh, Cheryl Lewis, Chul Ahn, Bret M. Evers, John D. Minna, Kathryn A. O'Donnell. Coordinated regulation of critical immune checkpoint proteins by the integrated stress response (ISR) pathway in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7528.

Comparing interplay effects in scanned proton therapy of lung cancer: Free breathing with various layer and volume rescanning versus respiratory gating with different gate widths

PurposeWe investigated interplay effects and treatment time (TT) in scanned proton therapy for lung cancer patients. We compared free-breathing (FB) approaches with multiple rescanning strategies and respiratory-gating (RG) methods with various gating widths to identify the superior irradiation technique. MethodsPlans were created with 4/1, 2/2, and 1/4 layered/volume rescans of FB (L4V1, L2V2, and L1V4), and 50%, 30%, and 10% gating widths of the total respiratory curves (G50, G30, and G10) of the RG plans with L4V1. We calculated 4-dimensional dynamic doses assuming a constant sinusoidal curve for six irradiation methods. The reconstructed doses per fraction were compared with planned doses in terms of dose differences in 99% clinical-target-volume (CTV) (ΔD99%), near-maximum dose differences (ΔD2%) at organs-at-risk (OARs), and TT. ResultsThe mean/minimum CTV ΔD99% values for FB were −1.0%/−4.9%, −0.8%/−4.3%, and −0.1%/−1.0% for L4V1, L2V2, and L1V4, respectively. Those for RG were −0.3%/−1.7%, −0.1%/−1.0%, and 0.0%/−0.5% for G50, G30, and G10, respectively. The CTV ΔD99% of the RGs with less than 50% gate width and the FBs of L1V4 were within the desired tolerance (±3.0%), and the OARs ΔD2% for RG were lower than those for FB. The mean TTs were 90, 326, 824, 158, 203, and 422 s for L4V1, L2V2, L1V4, G50, G30, and G10, respectively. ConclusionsFB (L4V1) is the most efficient treatment, but not necessarily the optimal choice due to interplay effects. To satisfy both TT extensions and interplay, RG with a gate width as large as possible within safety limits is desirable.

Optimal Treatment Strategy for Oligo-Recurrence Lung Cancer Patients with Driver Mutations.

The efficacy of local therapies for lung cancer patients with postoperative oligo-recurrence has been reported. However, whether local therapies should be chosen over molecular targeted therapies for oligo-recurrence patients with driver mutations remains controversial. Therefore, we aimed to investigate the optimal initial treatment strategy for oligo-recurrence in lung cancer patients with driver mutations. Among 2152 patients with lung adenocarcinoma who underwent surgical resection at our institute between 2008 and 2020, 66 patients with driver mutations who experienced cancer oligo-recurrence after surgery and were treated with local or molecularly targeted therapy as an initial therapy after recurrence were evaluated. Oligo-recurrence was characterized by the presence of 1 to 3 recurrent lesions. These patients were investigated, focusing on their post-recurrence therapies and prognoses. The median follow-up period was 71 months. Local and molecular targeted therapies were administered to 41 and 25 patients, respectively. The number of recurrence lesions tended to be lower in the initial local therapy group than in the molecular targeted therapy group. In the initial local therapy group, 23 patients (56%) subsequently received molecular targeted therapies. The time from recurrence to the initiation of molecular targeted therapy was significantly longer in the local therapy group than in the molecular targeted therapy group (p < 0.001). There was no significant difference in post-recurrence overall survival (hazard ratio, 1.429; 95% confidence interval, 0.701-2.912; log-rank, p = 0.324) and post-recurrence progression-free survival (hazard ratio, 0.799; 95% confidence interval, 0.459-1.390; log-rank, p = 0.426) in the initial local ablative therapy group compared with the initial molecular targeted therapy group. Local therapies as a first-line treatment did not show statistically significant differences in post-recurrence survival or progression-free survival compared with molecular targeted therapies. However, local therapies as an initial treatment should be considered preferably, as they can cure the recurrence and can delay the start of administration of molecular targeted therapies.

Induction of Arterial Inflammation by Immune Checkpoint Inhibitor Therapy in Lung Cancer Patients as Measured by 2-[18F]FDG Positron Emission Tomography/Computed Tomography Depends on Pre-Existing Vascular Inflammation.

Immune checkpoint inhibitors (ICI) are one of the most effective therapies in oncology, albeit associated with various immune-related adverse events also affecting the cardiovascular system. We aimed to investigate the effect of ICI on arterial 2-[18F]FDG uptake by using 2-[18F]FDG PET/CT imaging pre/post treatment in 47 patients with lung cancer. Maximum 2-[18F]FDG standardized uptake values (SUVmax) and target-to-background ratios (TBRs) were calculated along six arterial segments. We classified the arterial PET lesions by pre-existing active inflammation (cut-off: TBRpre ≥ 1.6). 2-[18F]FDG metabolic activity pre/post treatment was also quantified in bone marrow, spleen, and liver. Circulating blood biomarkers were additionally collected at baseline and after immunotherapy. ICI treatment resulted in significantly increased arterial inflammatory activity, detected by increased TBRs, in all arterial PET lesions analyzed. In particular, a significant elevation of arterial 2-[18F]FDG uptake was only recorded in PET lesions without pre-existing inflammation, in calcified as well as in non-calcified lesions. Furthermore, a significant increase in arterial 2-[18F]FDG metabolic activity after immunotherapy was solely observed in patients not previously treated with chemotherapy or radiotherapy as well as in those without CV risk factors. No significant changes were recorded in either 2-[18F]FDG uptake of bone marrow, spleen and liver after treatment, or the blood biomarkers. ICI induces vascular inflammation in lung cancer patients lacking pre-existing arterial inflammation.

Comparison study of clinic radiological profile of primary lung cancer using EDAS method

When bodily cells transform and proliferate out of control, it is called cancer. Cells are the minuscule building blocks that make up your body. Normal cells develop as required by the organism and degenerate when no longer required. The aberrant cells that make up cancer develop even if your body doesn't require them to. The aberrant cells in the majority of malignancies develop into a bump or mass known as a tumor. Long enough for cancer cells to exist in the body, they can spread (invade) into surrounding regions. They may even spread to various body regions (metastasis). Two key turning points for the practical application of targeted therapy in lung cancer patients were the sequencing of the malignant tumors genome and the development of medicines that target driver mutations. Understanding euplastic cells and mutational mechanisms, along with how they change as tumors form and how different cancer cells differ genetically, are all necessary for this. It is hoped that ongoing global initiatives to systematically identify the most pertinent genetic alterations for each subgroup of pulmonary cancer will raise the proportion of tumors that always respond better to novel medications targeting different genetic profiles. Oral medicines with significantly higher responder rates and lower toxicity than chemotherapy can be used to target many genetic changes. Methology: Alternative: Brain, Bone, Liver, Contra lateral lung, Adrenal gland. Evaluation Preference: Squamous cell carcinoma, denocarcinoma, Small cell lung carcinoma, undifferentiated carcinoma Result: As a result, Adrenal gland and top ranking, whereas the Brain rating received a low ranking received Conclusion: The value of the dataset for Lung cancer in EDAS method shows that it results in Adrenal gland and top ranking.

Alkylresorcinols as a New Type of Gut Microbiota Regulators Influencing Immune Therapy Efficiency in Lung Cancer Treatment

Background. Alkylresorcinols (ARs) are polyphenolic compounds of microbial origin with a wide spectrum of biological activities and are potentially involved in host immune functioning. The present study is aimed at evaluating alterations in AR content in blood serum and faeces from healthy donors and patients with lung cancer in connection with response to immune checkpoint inhibitor (ICI) therapy to estimate the regulatory potential of AR. Methods. Quantitative analysis of AR levels, as well as other microbial metabolites in blood serum and faeces, was performed using gas chromatography with mass spectrometric detection; estimation of lymphocyte subsets was performed by flow cytometry; faecal microbiota transplantation (FMT) from lung cancer patients after ICI therapy to germ-free mice was performed to explore whether the intestinal microbiota could produce AR molecules. Results. AR concentrations in both faeces and serum differ dramatically between healthy and lung cancer donors. The significant increase in AR concentrations in mouse faeces after FMT points to the microbial origin of ARs. For several ARs, there were strong positive and negative correlations in both faeces and serum with immune cells and these interrelationships differed between the therapy-responsive and nonresponsive groups. Conclusions. The content of ARs may influence the response to ICI therapy in lung cancer patients. ARs may be considered regulatory molecules that determine the functioning of antitumor immunity.

The Effects of Antibiotics on the Development and Treatment of Non-Small Cell Lung Cancer.

There have been studies on antibiotic use concerning lung cancer and its potential impact on carcinogenesis and microbiome. However, subsequent research has failed to support these associations consistently. In terms of the potential carcinogenic of antibiotics on lung cancer, the available evidence has not been sufficient to draw any definitive conclusions. Maintaining immune homeostasis and preventing pathogen invasion is critically dependent on the microbiome. The subtle balance of the body microbiota, including the lungs, is susceptible to disruption by antibiotic use. There is an association between disruptions of the lung microbiome and respiratory diseases, including lung cancer, and decreased efficacy of treatments. Patients with lung cancer are often indicated for antibiotic treatment due to respiratory infections or other comorbidities. Pulmonary infections in the area of undetected lung tumors are not uncommon. They can be an early sign of malignancy, which may explain the association between antibiotic use and lung cancer diagnosis. Antibiotic use can also affect the effectiveness of immune checkpoint inhibitor therapy. Studies suggest that antibiotic use can impair the efficacy of immune checkpoint inhibitor therapy in lung cancer patients, particularly around the time when treatment is initiated. These findings require further study, understanding underlying mechanisms, and identifying microbiota signatures associated with treatment response.

Progress in the Prevention of Complications of Interventional Therapy in Patients with Lung Cancer Hemoptysis

Lung cancer is the malignant tumor with the highest incidence and mortality in our country and even in the world. The radical rate of conventional therapy, such as simple radiotherapy, chemotherapy, operation, traditional Chinese medicine treatment is low and the effect is not ideal. Bronchial lung cancer is one of the most common causes of massive hemoptysis. Vascular interventional therapy has become the first choice in clinical treatment of acute massive hemoptysis. Interventional therapy for lung cancer patients, as a safe, efficient, minimally invasive and economical treatment, has been widely used at home and abroad. However, due to inadequate patient assessment, equipment may not be advanced enough, and treatment techniques need to be developed, more or less postoperative complications associated with interventional therapy may occur. This article reviews the research status of interventional therapy and complication prevention in patients with lung cancer hemoptysis as follows.

Artificial Intelligence and Lung Cancer: Impact on Improving Patient Outcomes

Lung cancer remains one of the leading causes of cancer-related deaths worldwide, emphasizing the need for improved diagnostic and treatment approaches. In recent years, the emergence of artificial intelligence (AI) has sparked considerable interest in its potential role in lung cancer. This review aims to provide an overview of the current state of AI applications in lung cancer screening, diagnosis, and treatment. AI algorithms like machine learning, deep learning, and radiomics have shown remarkable capabilities in the detection and characterization of lung nodules, thereby aiding in accurate lung cancer screening and diagnosis. These systems can analyze various imaging modalities, such as low-dose CT scans, PET-CT imaging, and even chest radiographs, accurately identifying suspicious nodules and facilitating timely intervention. AI models have exhibited promise in utilizing biomarkers and tumor markers as supplementary screening tools, effectively enhancing the specificity and accuracy of early detection. These models can accurately distinguish between benign and malignant lung nodules, assisting radiologists in making more accurate and informed diagnostic decisions. Additionally, AI algorithms hold the potential to integrate multiple imaging modalities and clinical data, providing a more comprehensive diagnostic assessment. By utilizing high-quality data, including patient demographics, clinical history, and genetic profiles, AI models can predict treatment responses and guide the selection of optimal therapies. Notably, these models have shown considerable success in predicting the likelihood of response and recurrence following targeted therapies and optimizing radiation therapy for lung cancer patients. Implementing these AI tools in clinical practice can aid in the early diagnosis and timely management of lung cancer and potentially improve outcomes, including the mortality and morbidity of the patients.

Metformin induces ferroptosis through the Nrf2/HO-1 signaling in lung cancer

BackgroundMetformin is the most frequently prescribed medication for the treatment of type II diabetes mellitus and has played an anti-tumor potential in a variety of cancer types. Metformin can inhibit the growth of many cancer cells through various mechanisms, including ferroptosis. However, it is still unclear whether metformin can induce ferroptosis in lung cancer.MethodsThis study evaluated the anti-tumor effect of metformin by detecting the levels of oxidative stress factors, the levels of ferrous ions, and the expression of ferroptosis-related genes in A549 and H1299 lung cancer cell lines treated with or without metformin.ResultsThe results showed that metformin treatment increased the levels of MDA, ROS and iron ions, while decreased the levels of GSH, T-SOD and CAT. Meanwhile, metformin treatment reduced the protein expression levels of Gpx4 and SLC7A11, Nrf2 and HO-1, while the addition of ferroptosis inhibitor ferrostatin-1 reversed the reduction.ConclusionsThese results demonstrated that metformin exerts anti-tumor effects by inducing ferroptosis through the Nrf2/HO-1 signaling pathway in lung cancer cells, providing a theoretical basis for drug therapy of lung cancer patients.

Longitudinal high-dimensional analysis identifies immune features associating with response to anti-PD-1 immunotherapy

Response to immunotherapy widely varies among cancer patients and identification of parameters associating with favourable outcome is of great interest. Here we show longitudinal monitoring of peripheral blood samples of non-small cell lung cancer (NSCLC) patients undergoing anti-PD1 therapy by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines measurements. We find that higher proportions of circulating CD8+ and of CD8+CD101hiTIM3+ (CCT T) subsets significantly correlate with poor clinical response to immune therapy. Consistently, CD8+ T cells and CCT T cell frequencies remain low in most responders during the entire multi-cycle treatment regimen; and higher killer cell lectin-like receptor subfamily G, member 1 (KLRG1) expression in CCT T cells at baseline associates with prolonged progression free survival. Upon in vitro stimulation, CCT T cells of responders produce significantly higher levels of cytokines, including IL-1β, IL-2, IL-8, IL-22 and MCP-1, than of non-responders. Overall, our results provide insights into the longitudinal immunological landscape underpinning favourable response to immune checkpoint blockade therapy in lung cancer patients.

Clinical evaluation of synthetic computed tomography methods in adaptive proton therapy of lung cancer patients.

Efficient workflows for adaptive proton therapy are of high importance. This study evaluated the possibility to replace repeat-CTs (reCTs) with synthetic CTs (sCTs), created based on cone-beam CTs (CBCTs), for flagging the need of plan adaptations in intensity-modulated proton therapy (IMPT) treatment of lung cancer patients. Forty-two IMPT patients were retrospectively included. For each patient, one CBCT and a same-day reCT were included. Two commercial sCT methods were applied; one based on CBCT number correction (Cor-sCT), and one based on deformable image registration (DIR-sCT). The clinical reCT workflow (deformable contour propagation and robust dose re-computation) was performed on the reCT as well as the two sCTs. The deformed target contours on the reCT/sCTs were checked by radiation oncologists and edited if needed. A dose-volume-histogram triggered plan adaptation method was compared between the reCT and the sCTs; patients needing a plan adaptation on the reCT but not on the sCT were denoted false negatives. As secondary evaluation, dose-volume-histogram comparison and gamma analysis (2%/2mm) were performed between the reCT and sCTs. There were five false negatives, two for Cor-sCT and three for DIR-sCT. However, three of these were only minor, and one was caused by tumour position differences between the reCT and CBCT and not by sCT quality issues. An average gamma pass rate of 93% was obtained for both sCT methods. Both sCT methods were judged to be of clinical quality and valuable for reducing the amount of reCT acquisitions.

Multi-institutional survey of antiemetic therapy in lung cancer patients treated with carboplatin in Hokushin region

ObjectiveAppropriate monitoring and management of chemotherapy-induced nausea and vomiting (CINV) with prophylactic antiemetics is important for cancer patients. This study was performed to validate the clinical practice of antiemetic use with carboplatin-based chemotherapy in lung cancer patients in the Hokushin region (Toyama, Ishikawa, Fukui, and Nagano prefectures), Japan.MethodsWe surveyed retrospective data of newly diagnosed and registered lung cancer patients initially treated with carboplatin-based chemotherapy in 21 principal hospitals in the Hokushin region linked with health insurance claims data between 2016 and 2017.ResultsA total of 1082 lung cancer patients (861 [79.6%] men, 221 [20.4%] women; median age 69.4 years [range, 33–89 years]). All patients received antiemetic therapy, with 613 (56.7%) and 469 patients (43.3%) receiving 5-hydroxytryptamine-3 receptor antagonist/dexamethasone double regimen and 5-hydroxytryptamine-3 receptor antagonist/dexamethasone/neurokinin-1 receptor antagonist triple regimen, respectively. However, the rates of double regimen and use of palonosetron were higher in Toyama and Fukui prefectures. Thirty-nine patients (3.6%) changed from double to triple regimen, while 41 patients (3.8%) changed from triple to double regimen after the second cycle, but six of these returned to triple antiemetics in subsequent cycles.ConclusionAdherence to antiemetic guidelines in clinical practice was high in Hokushin region. However, rates of double and triple antiemetic regimens differed between the four prefectures. Simultaneous analysis of nationwide registry and insurance data was valuable for evaluating and comparing the differences in the status of antiemesis and management.

OC-0444 Clinical feasibility of synthetic CTs for adaptive proton therapy in lung cancer patients

OC-0444 Clinical feasibility of synthetic CTs for adaptive proton therapy in lung cancer patients

Consensus-based failure mode and effect analysis in group decision-making with incomplete weights of risk factors: Case study of stereotactic body radiation therapy for lung cancer

Failure mode and effect analysis (FMEA) is a widely used management technique to identify potential failure modes in products, processes, systems, and services to assign limited resources for implementing improvement efforts. For the FMEA with a number of experts, the experts may take different influences on the decision-making process due to the difference between individual rationality and cognition and the influence of social relations. Besides, incomplete weights of risk factors are vital to capturing the fuzziness of experts’ evaluation. Therefore, this paper proposes a consensus-based FMEA method to explore that how cooperative relationship network of experts, the consensus process, and incomplete weight information of risk factors in FMEA influence the decision-making process. First, a consensus reaching process considering cooperative relationships between experts, the self-confidence of experts, and minimum adjustment of expert opinion is proposed to derive a collective evaluation of group. Afterward, the stochastic multicriteria acceptability analysis method is integrated with the gained and lost dominance score method to deal with incomplete weights of risk factors in the FMEA. The proposed method is employed in a case study about ranking the failure modes of stereotactic body radiation therapy for lung cancer patients. The robustness and feasibility of the proposed method are validated by comparative analysis.