Japan Lung Cancer Society Research Articles

Comprehensive analysis of predictive factors for efficacy in concurrent chemo-radiotherapy for locally advanced non-small cell lung cancer, utilizing individual patient data from the Japan lung cancer society integrated clinical trial database: Is there room for further improvement?

8043 Background: The standard treatment for unresectable, locally advanced NSCLC is concurrent chemoradiotherapy followed by durvalumab. While the effectiveness of chemoradiotherapy is pivotal, the exploration into predictive factors of the efficacy is notably limited. Methods: The Japanese Lung Cancer Society (JLCS) integrated eight randomized Phase II/III trials (JCOG9812, JCOG0301, NJLCG0601, OLCSG0007, SPECTRA, TORG1018, WJOG5008L, WJTOG0105) concerning chemoradiotherapy for locally advanced NSCLC, constructing the JLCS Integrated Clinical Trial Database (JIDB), with individual data of 1288 patients. This study analyzed 1162 patients who underwent concurrent chemoradiotherapy, focusing on factors impacting PFS. A logistic regression with the least absolute shrinkage and selection operator (LASSO) analyses for 3-yr PFS were performed, and the five most related factors were further evaluated using the Kaplan-Meier method and log-rank tests. The impact of pneumonitis and esophagitis on PFS was also explored. Results: Age [median (Q1;Q3)]; 64 (57;71), male/female; 961/201, Ad/Sq/Oth; 580/446/134, PS 0/1/2; 562/578/5, stage IIIA/IIIB; 468/694, T factor 4/3/2/1/0; 436/158/341/156/3, N factor 3/2/1/0; 300/692/44/62, PS 0/1/2; 562/578/5, primary site; upper, middle/lower lobe; 599/161, BMI; 21.8 (19.7;24.0), weight loss (≥5% within 6m) yes/no; 135/644, LDH (IU/l); 203 (175;276), CRP (mg/dl); 0.70 (0.20;2.60), irradiated dose (Gy); 60 (60;60), combined regimen; platinum/taxane 303, CDDP/mitomycin/vindesine; 254, CDDP/5-FU-based; 196, CDDP/vinorelbine 87, CDDP/pemetrexed 50, others 272. The median PFS in all patients was 9.72m (95% CI; 9.33 – 10.38), with 3-yr, 5-yr, and 10-yr PFS rates of 19.7, 14.3, 10.1%. LASSO logistic regression identified Sq, lower lobe primary, age, pack-years, and weight loss as the top negative influencers. The PFS curve was significantly shorter in patients with lower lobe primary (median of 8.15 vs. 9.46m, p = 0.023) and weight loss (median of 7.29 vs. 9.72m, p < 0.0001). Pneumonitis occurred in 50.9% (grade≥3 in 6.7%) and esophagitis in 41.9% (grade≥3 in 3.9%). Grade≥2 pneumonitis shortened PFS (8.2 vs. 10.2m, p = 0.00015), while, unexpectedly, grade≥1 esophagitis was associated with longer PFS (12.9 vs. 8.6m, p < 0.0001). Conclusions: The efficacy of concurrent chemoradiotherapy varies significantly based on the primary site. Weight loss is a significant predictor of efficacy, as is in metastatic disease. The impact of pneumonitis and esophagitis suggest that modifying lung and esophageal irradiation might enhance treatment efficacy. Further research in this area is still certainly warranted.

Creation of an Integrated Clinical Trial Database and Data Sharing for Conducting New Research by the Japan Lung Cancer Society

Creation of an Integrated Clinical Trial Database and Data Sharing for Conducting New Research by the Japan Lung Cancer Society

Epidemiology, risk factors and impact of cachexia on patient outcome: Results from the Japanese Lung Cancer Registry Study.

Cancer cachexia is a syndrome that does not fully recover with nutritional support and causes appetite loss and body weight loss. It worsens a patient's quality of life and prognosis. In this study, the epidemiology of cachexia in lung cancer, its risk factors and its impact on chemotherapy response rate and prognosis were examined using the national database of the Japan Lung Cancer Society. Understanding these things related to cancer cachexia is important as a starting point in overcoming cancer cachexia in patients with lung cancer. In 2012, 12320 patients from 314 institutions in Japan were registered in a nationwide registry database (Japanese Lung Cancer Registry Study). Of these, data on body weight loss within 6months were available for 8489 patients. We defined the patients with body weight loss≥5% within 6months, which is one of the three criteria listed in the 2011 international consensus definition of cancer cachexia, as cachectic in this study. Approximately 20.4% of the 8489 patients had cancer cachexia. Sex, age, smoking history, emphysema, performance status, superior vena cava syndrome, clinical stage, site of metastasis, histology, epidermal growth factor receptor (EGFR) mutation status, primary treatment method and serum albumin levels were significantly different between patients with and without cachexia. Logistic analyses showed that smoking history, emphysema, clinical stage, site of metastasis, histology, EGFR mutation, serum calcium and albumin levels were significantly associated with cancer cachexia. The response to initial therapy, including chemotherapy, chemoradiotherapy or radiotherapy, was significantly poorer in the patients with cachexia than in those without cachexia (response rate: 49.7% vs. 41.5%, P<0.001). Overall survival was significantly shorter in the patients with cachexia than in those without cachexia in both univariate and multivariable analyses (1-year survival rate: 60.7% vs. 37.6%, Cox proportional hazards model, hazard ratio: 1.369, 95% confidence interval: 1.274-1.470, P<0.001). Cancer cachexia was seen in approximately one fifth of the lung cancer patients and was related to some baseline patient characteristics. It was also associated with a poor response to initial treatment, resulting in poor prognosis. The results of our study may be useful for early identification and intervention in patients with cachexia, which may improve their response to treatment and their prognosis.

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: A Study on the Cytomorphological Characteristics of "atypical cells" Category

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: A Study on the Cytomorphological Characteristics of "atypical cells" Category

P60-1 Safety and feasibility of hyper short-hydration using furosemide in cisplatin-based chemotherapy

In recent years, short-hydration method has been widely adopted when administrating cisplatin-based chemotherapy, especially in outpatient setting. In this study, we assessed the safety of a hyper short-hydration method using furosemide, which requires shorter administration time than that proposed by The Japan Lung Cancer Society.

Creation of an Integrated Clinical Trial Database and Data Sharing for Conducting New Research by the Japan Lung Cancer Society

IntroductionAlthough data accumulated in clinical trials have higher accuracy compared with real-world data and are irreplaceably valuable, most previous clinical trial data have been left unused. MethodsThe Japan Lung Cancer Society (JLCS) asked six clinical trial groups that conducted randomized clinical trials on curative chemoradiation for locally advanced NSCLC to provide data. After obtaining consent from all six groups, data were collected from August 2019 to June 2021. ResultsA total of eight trials, JCOG9812, JCOG0301, NJLCG0601, OLCSG0007, WJTOG0105, WJOG5008L, SPECTRA, and TORG1018, were included. More than 3000 data items were integrated into 408 items by adjusting their definitions and units. The total number of collected cases was 1288: median age (range), 66 (30–93) years; sex (male/female) 1064/224; pathological type (squamous cell carcinoma, adenocarcinoma, other NSCLC, and unknown) 517, 629, 138, and 4; and stage IIIA and B, 536 and 752. The median overall survival was 26.0 months, with 2-, 5-, and 10-year survival rates of 53.7%, 24.8%, and 15.2%, respectively, in all enrollments. The median progression-free survival was 9.6 months, with 2-, 5-, and 10-year progression-free survival rates of 23.6%, 14.0%, and 9.4%, respectively. Part of the information in the database has been made available on the JLCS web page, and the JLCS members were provided the right to propose research using the database. ConclusionsThe integration and sharing of clinical trial data for research purposes was made real by the nonprofit, academic organization, the JLCS. This database will lead to innovative researches and contribute to the improvement of lung cancer treatment and future research.

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and the Japanese Society of Clinical Cytology: An Extensive Study Containing More Benign Lesions

Introduction: The Japan Lung Cancer Society (JLCS) and the Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma (JLCS-JSCC system). Prior to the proposal, the Papanicolaou Society of Cytopathology (PSC) had proposed a revised reporting system (PSC system), which comprises the “neoplastic, benign neoplasm, and low-grade carcinoma” category (N-B-LG category), in addition to the 4 categories of the JLCS-JSCC system. This study aimed to evaluate the interobserver agreement of the JLCS-JSCC system with an additional dataset with more benign lesions in comparison with the PSC system. Methods: We analyzed 167 cytological samples, which included 17 benign lesions, obtained from the respiratory system. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the JLCS-JSCC system and PSC system. Results: The interobserver agreement was moderate in the JLCS-JSCC (k = 0.499) and PSC (k = 0.485) systems. Of the 167 samples, 17 samples were benign lesions: 7 pulmonary hamartomas, 5 sclerosing pneumocytomas, 2 squamous papillomas, one solitary fibrous tumor, one meningioma, and one lymphocytic proliferation. There were diverse sample types as follows: 11 touch smears, 3 brushing smears, 2 aspirations, and one sputum sample. Fourteen samples (82.3%) were categorized into “negative” or “atypical” by more than half of the observers in the JLCS-JSCC system. Conversely, 3 samples were categorized as “suspicious” or “malignant” by more than half of the observers in the JLCS-JSCC system. On the other hand, 11 samples (64.7%) were categorized into the N-B-LG category by more than half of the observers in the PSC system. Conclusions: The concordance rate in the JLCS-JSCC system was slightly higher than that in the PSC system; however, the interobserver agreement was moderate in both the JLCS-JSCC and PSC systems. These results indicate that both the JLCS-JSCC and PSC systems are clinically useful. Therefore, both systems are expected to have clinical applications. It may be important to integrate the 2 systems and construct a universal system that can be used more widely in clinical practice.

METex14 Skipping Testing Guidance for Lung Cancer Patients: The Guidance from the Biomarker Committee, the Japan Lung Cancer Society

METex14 Skipping Testing Guidance for Lung Cancer Patients: The Guidance from the Biomarker Committee, the Japan Lung Cancer Society

P10.09 Efficacy and Toxicity of EGFR-TKI in Frail NSCLC with EGFR Mutation: A Retrospective Analysis in a Single Institution

EGFR-TKI is the standard treatment of care for sensitizing EGFR mutation-positive advanced non-small lung cancer (NSCLC) patients. However, the treatment strategy of first-line EGFR-TKI for frail patients has not been well established yet. In current NCCN guideline, osimertinib is preferred as first-line therapy for sensitizing EGFR mutation-positive patients regardless of their age and ECOG performance status (PS), while Japan Lung Cancer Society guideline 2020 recommends first generation EGFR-TKIs for the patients with PS 2-4.

The 61st Annual Meeting of the Japan Lung Cancer Society: Eradication of lung cancer 2020

The 61st Annual Meeting of the Japan Lung Cancer Society: Eradication of lung cancer 2020

System for thymic disease research and clinical practice in Japan.

Japanese Association for Research of the Thymus (JART) established by emeritus professor Akira Masaoka is a cross-sectional association of physicians and researchers and have worked in clinical and basic research on thymic neoplasms and thymus-related diseases in collaboration with The Japanese Surgical Society (JSS), Japanese Association for Chest Surgery (JACS), Japanese Association for Thoracic Surgery (JATS), Japan Lung Cancer Society (JLCS), Japanese Respiratory Society (JRS) and Japanese Association for Respiratory Endoscopy (JARE). JART has performed several clinical trials, and the most important establishment of JART in recent days is the project of the nation-wide retrospective database of thymic epithelial tumors, which contributed to UICC TNM staging. Currently, JART is building the prospective database in collaboration with the Japanese Joint Committee for Lung Cancer Registry (JJCLCR).

Importance of doctor-initiated management of the balance between work and treatment for lung cancer patients: Results of a nationwide survey by the Japan Lung Cancer Society.

BackgroundsSince the recent development of molecular targeted drugs and immune checkpoint inhibitors has improved lung cancer treatment options and outcomes, supporting patients in balancing work and pharmacotherapy have become even more important in the field of lung cancer treatment. This study sought to identify the current status and roles of doctors in balancing work and treatment for lung cancer patients.MethodsPatients and doctors were recruited to complete a web‐based questionnaire survey by the Japan Lung Cancer Society.ResultsAbout 287 lung cancer patients and 381 doctors were included in the analysis. About 42.9% of patients responded that “there was no discussion” about their working conditions or work before the initiation of pharmacotherapy, while 22.6% responded that “there was an inquiry from a doctor/health care provider and a discussion that included the doctor was held.” About 45.3% of patients took leave or resigned from work at the time of diagnosis. The most common reasons for patients to resign before or during pharmacotherapy were “poor physical condition due to side effects of treatment or illness” and “concern about causing problems in the workplace.” To assist in balancing work and pharmacotherapy, patients desired “increased opportunities to consult about work” (36.9%) and “provision of treatment options with few adverse events” (28.9%).ConclusionThis study highlights the importance of doctor‐initiated management of the balance between work and treatment for lung cancer patients. An important first step is for doctors themselves to take an interest in their patients' professions and initiate discussions of work‐related topics with their patients.

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and Japanese Society of Clinical Cytology: An Interobserver Reproducibility Study and Risk of Malignancy Evaluation on Cytology Specimens

Introduction: The classification of lung carcinoma is based on small biopsies and/or cytology in 80% of patients with non-small cell carcinoma. However, there is no widely accepted classification system for respiratory cytology. The Japan Lung Cancer Society (JLCS) and Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma with the following categories: (1) “negative for malignancy,” (2) “atypical cells,” (3) “suspicious for malignancy,” and (4) “malignancy.” Objective: The aim of this work was to perform an interobserver reproducibility study to confirm the utility of the four-tiered reporting system on respiratory cytological samples. Methods: We analyzed 90 cytological samples obtained with bronchoscopy. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the three-, four-, and five-tiered reporting systems. Results: The interobserver agreement was fair in the three- (κ = 0.50), four- (κ = 0.45), and five-tiered (κ = 0.45) reporting systems. However, the four-tiered reporting system provided more precise information than the three-tiered reporting system in patient management. The risk of malignancy in the four-tiered reporting system was also stratified well: 19.3% for “negative for malignancy,” 45.6% for “atypical cells,” 74.7% for “suspicious for malignancy,” and 88.1% for “malignancy.” Conclusions: The reporting system proposed by the JLCS and JSCC was designed to enhance the communication between clinicians and pathologists and among different institutions. It is simple and applicable to cytological diagnosis of any respiratory diseases. We propose establishing an international classification for respiratory cytology, harmonizing the reporting systems proposed by different countries.

Abstract 752: Rapid acquired resistance to alectinib in ALK-positive lung cancers with high tumor mutation burden

Abstract Background: Alectinib, a highly selective anaplastic lymphoma kinase (ALK) inhibitor, demonstrates an unprecedented effect in ALK-positive lung cancers. However, some tumors quickly develop resistance to alectinib. In this study, we aimed to investigate the mechanism of the rapidly acquired resistance to alectinib using clinical samples. Methods: Autopsied specimens of lung, liver, and renal tumors were obtained from a 51-year-old male patient with advanced ALK-positive lung cancer, who had acquired resistance to alectinib in only three months. Two alectinib-resistant cell lines were established from pleural effusion (ABC-14) or liver tumors (ABC-17). A patient-derived xenograft (PDX) model was also developed from liver tumors. Next-generation sequencing (NGS), direct DNA sequencing, and quantitative real time reverse transcription-PCR were performed. Results: ABC-14 harbored no ALK mutations and showed sensitivity to crizotinib, an ALK/MET inhibitor. It also showed mesenchymal-epithelial transition factor (MET) gene amplification and amphiregulin overexpression. The combination of crizotinib and erlotinib showed beneficial inhibitory effects on cell growth. ABC-17 and PDX tumors harbored ALK G1202R. PDX tumors metastasized to multiple organs in vivo, whereas lorlatinib, the third-generation ALK inhibitor, diminished tumor growth both in vitro and in vivo. NGS demonstrated high tumor mutation burden (TMB) and heterogeneous evolution of the patient tissues. The autopsied lung tumors harbored ALK G1202R (c. 3604 G&amp;gt;A) and the right renal metastasis harbored ALK G1202R (c. 3604 G&amp;gt;C); the mutation thus altered codon sequences. Conclusions: High TMB and heterogeneous tumor evolution may have conferred the rapid resistance to alectinib. Timely administration of lorlatinib or combination therapies with an ALK inhibitor and other RTK inhibitors may constitute a potent therapeutic strategy. Financial support: This research was supported by a Grant for Lung Cancer Research (K.O.), provided by the Japan Lung Cancer Society. Citation Format: Kadoaki Ohashi, Go Makimoto, Shuta Tomida, Kazuya Nishii, Shinichi Toyooka, Katsuyuki Kiura. Rapid acquired resistance to alectinib in ALK-positive lung cancers with high tumor mutation burden [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 752.

Retrospective study of efficacy of adjuvant chemotherapy using tegafur-uracil in patients with non-small cell lung cancer with primary tumor size of 4.1-5.0 cm.

The staging of patients with a tumor of diameter 4.1-5.0 cm and no lymphatic/distant metastases have been up-graded to stage IIA in the latest 8th edition of the TNM staging system. However, the efficacy of adjuvant tegafur-uracil (UFT) therapy in these patients, which has been recommended in the guideline issued by The Japan Lung Cancer Society, remains unclear. We evaluated the efficacy of adjuvant UFT therapy among a cohort by retrospective analyses of multicentric database. In 2005-2007, 130 patients with p-stage IB non-small cell lung cancer (NSCLC) (diagnosed according to the 7th edition of the TNM staging system) and tumor size of ≥3.1 cm underwent anatomic complete resection at nine of our affiliated hospitals. We retrospectively reviewed the clinicopathological characteristics and the outcomes among these patients. Ninety-eight patients had tumor size of 3.1-4.0 cm (T2a group), whereas 32 patients had tumor size >4.0 cm (T2b group). Overall, patients who received adjuvant UFT showed a tendency of better outcomes than patients who did not [hazard ratio (HR) 0.564; 95% confidence interval (CI), 0.257-1.238, P=0.147]. In subgroup analyses, patients who received adjuvant UFT also tended to show better outcomes than those who did not in both T2a group and T2b group (HR 0.504; 95% CI, 0.202-1.255, P=0.132 in T2a group and HR 0.855; 95% CI, 0.181-4.033, P=0.843 in T2b group, respectively). Our results suggest that adjuvant UFT therapy have the potential to improve postoperative outcomes even in patients with p-stage IIA disease, as classified according to the 8th edition of the TNM staging system.

The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV

According to rapid development of chemotherapy in advanced non-small cell lung cancer (NSCLC), the Japan Lung Cancer Society has been updated its own guideline annually since 2010. In this latest version, all of the procedure was carried out in accordance with grading of recommendations assessment, development and evaluation (GRADE) system. It includes comprehensive literature search, systematic review, and determination of the recommendation by multidisciplinary expert panel which consisted of medical doctors, pharmacists, nurses, statisticians, and patients from patient advocacy group. Recently, we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors. Thus, the guideline proposes to categorize patients into three entities: (1) driver oncogene-positive, (2) PD-L1 ≥ 50%, and (3) others. Based on this subgroup, 31 clinical questions were described. We believe that this attempt enables clinicians to choose appropriate treatment easier. Here, we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC, stages IV.

Addressing the challenge of proper delineation of lymph node stations in modern radiotherapy for lung cancer.

We greatly appreciate the recent publication of a Japan Lung Cancer Society and Japanese Society for Radiation Oncology consensus-based computed tomographic atlas for defining regional lymph node stations (LNSs) for radiotherapy for lung cancer. This atlas is based on the International Association for the Study of Lung Cancer (IASLC) consensus lymph node map, which resolved differences between the Japanese and American classification and was incorporated into the seventh edition of the TNM staging system. The authors must be commended for providing a very clear, comprehensive presentation of the borders of the mediastinal and hilar LNSs, using a multidisciplinary approach. The Atlas created by Itazawa et al. is the second published consensus-based atlas for defining the LNSs for lung cancer radiotherapy according to the IASLC-endorsed LNS map. The differences between the two published atlases of LNS delineation in radiation oncology are discussed.

JLCS medical practice guidelines for thymic tumors: summary of recommendations.

The Guideline Committee of the Japan Lung Cancer Society (JLCS) for Thymic Tumors published the Medical Practice Guideline for Thymic Tumors in Japanese as Chapter 3 of the Medical Practice Guidelines for Lung Cancers according to evidence-based medicine in December 2016. This medical practice guideline is the first for thymic epithelial tumors in Japan, and comprises a set of recommendations covering clinical diagnosis, treatment and pathological diagnosis. Thymic epithelial tumors include thymoma, thymic carcinoma and thymic neuroendocrine tumor. The recommendations for clinical diagnosis concern detection of the symptoms, blood and serum tests according to clinical presentation, essential imaging for differential diagnosis and staging, and the necessity and methods of definitive diagnosis. The recommendations for treatment are dependent on tumor stage and recurrence status, and the treatment modalities included surgery, radiation therapy, chemotherapy and multimodality therapy. Those for pathological diagnosis deal with the handing methods of resected specimen and essential reporting contents for pathological diagnosis. Since data from large-scale analyses or clinical studies of thymic epithelial tumor are limited due to its low prevalence, the relevant recommendations and grading were based on available reported evidence and expert opinions as well as diagnostic methods and treatments commonly used in Japan. This report summarizes the recommendations concerning each topic addressed by this JLCS guideline for thymic tumors.

Effect of nationwide palliative care education program on lung cancer specialists.

e21715 Background: Although palliative care has owed an essential part of cancer treatment, palliative care specialists are still insufficient. Thus in Japan, the Palliative care Emphasis program on symptom management and Assessment for Continuous Medical Education (PEACE) was launched in 2008 to provide primary palliative care education for all physicians engaged in cancer treatment. However, the effect of PEACE program on participants was uncertain. Methods: We conducted web-based surveys for physicians belonging to the Japan Lung Cancer Society and assessed outcomes of the PEACE program across three domains: knowledge, practices, and difficulties regarding palliative care by using the palliative care knowledge questionnaire for PEACE (PEACE-Q), Palliative Care self-reported Practice Scale (PCPS), and the Palliative Care Difficulties Scale (PCDS), respectively. All of these instruments were already validated in previous studies. Results: In February 2015, the survey was distributed to 5300 physicians and 923 of those surveyed including 455 respiratory physicians, 345 pulmonary surgeons, and 35 medical oncologist responded to all questionnaires. The result of PEACE-Q, PCPS, and PCDS (low score is better) were significantly superior in physicians who had participated in the PEACE program (n = 519) compared with non-participants (n = 404) (28.0 vs. 24.5, 71.8 vs. 67.1, and 34.4 vs. 36.9, respectively). The PEACE participants made significantly better scores than non-participants in all domains of PEACE-Q (philosophy of palliative care, cancer pain, side effects of opioids, dyspnea, nausea and vomiting, psychological distress, delirium, communication, and community-based palliative care) and PCPS (pain, dyspnea, delirium, dying-phase care, communication, and patient- and family-centered care), and 3 domains of PCDS (alleviation of symptoms, expert support, and communication with the patient and family). Conclusions: The PEACE program improved knowledge and practice of palliative care in lung cancer specialists in Japan.

Abstract P040: Quitting Smoking Reduces Lectin-like Low-density Lipoprotein Receptor-1 index, an Independent Cardiovascular Risk Marker of Vascular Inflammation

Background: Vessel walls Inflammation is involved in the destabilization of atherosclerotic plaques. Lectin-like low-density lipoprotein (LDL) receptor-1 (LOX-1) is an oxidized LDL receptor expressed in vascular cells and monocytes. The LOX index is calculated by multiplying the concentration of LOX-1 ligand containing apolipoprotein B with the concentration of soluble LOX-1. A high LOX index reflects an increased risk for stroke and myocardial infarction. Fortunately, the cardiovascular risk decreases within 2 years after smoking cessation. However, no study has investigated the potential of the LOX index as a cardiovascular risk marker in smokers, and the relationship between the LOX index and smoking cessation. Purpose: The present study investigated the change of cardiovascular risk marker, LOX index, after smoking cessation and the relationship between smoking-related factors and LOX index. In addition, the present study investigated the impact of smoking cessation on the LOX index. Methods: Relation of the clinical parameters to the LOX index was examined on 207 subjects (155 males and 52 females) at the first visit to our outpatient clinic for smoking cessation. All anti-smoking treatments were conducted according to the Standard Procedures for Anti-Smoking Treatment (originally issued in March 2006 by the Japanese Circulation Society, Japan Lung Cancer Society, and Japanese Cancer Association). The patients were treated with transdermal nicotine patches or the oral administration of varenicline. Among patients who attended our smoking cessation clinic, 94 subjects (62 males and 32 females) successfully quit smoking. We determined their LOX index at baseline on their first visit and repeated it 3 months after beginning smoking cessation to assess the impact of smoking cessation on the LOX index. Results: Sex-adjusted regression analysis and multivariate analysis identified three independent determinants of the LOX index, namely low-density lipoprotein-cholesterol (LDL-C; β = 0.273, p = 0.002), high-sensitivity C-reactive protein (β = 0.324, p &amp;lt; 0.001), and expired carbon monoxide concentration reflecting the amount of smoking (β = 0.225, p = 0.008). Body mass index (BMI) significantly increased 3 months after the onset of smoking cessation (p &lt; 0.001). However, the LOX index significantly decreased from baseline to 3 months (from 3.31 to 2.57; p &amp;lt; 0.001), regardless of the rate of increase in BMI post-cessation. Conclusions: The LOX index is closely associated with hsCRP, a common inflammatory marker, suggesting that LOX-1 is involved in cardiovascular events by inducing vessel wall inflammation. Our results also suggest that the LOX index is useful for evaluating the effects of smoking cessation intervention on cardiovascular risk reduction. In addition, smoking cessation may induce a decrease in this cardiovascular risk marker, independently of weight gain.