bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends and survival of malignant mesothelioma across racial groups between 2000-2019: A real-world study.
Authors: Al Armashi Abdul Rahman , Alkrekshi Akram , Al Zubaidi Anas , Hammad Faris , Elantably Dina , Mahmood Omar , Truong Vien , Ngo Tam N.M. , Bruno Debora S.
Published: June 2023

e20539

Background: Malignant mesothelioma of the pleura (MMP) is a rare and aggressive malignancy and predominantly affects patients of White race in the U.S. Despite treatment advancements, the 5-year survival rate remains between 5% and 10%. Studies assessing racial disparities in MMP are lacking. We conducted a retrospective study to evaluate prevalence, survival and mortality trends among racial groups. Methods: We used the SEER database to determine the racial prevalence of all histological subtypes of MMP between 2000 and 2019. We calculated racial and histological subtype survival Cox proportional hazard ratios while controlling for age, gender, ethnicity, surgery, chemotherapy, and radiation use. Second, we used the CDC WONDER database to identify all mesothelioma deaths for the same period. Age-adjusted mortality (AAM) rates per 100,000 persons were standardized to 2000 US census data and stratified by race. Results: A total of 12791 patients were identified, mostly White (95%), followed by Blacks (%5) and Asians (0.4%). The percentages of patients with epithelioid, sarcomatoid and biphasic histologies were as follows: Whites (67.6%, 19.2%, 13.2%), Blacks (70.4%, 19.4%, 10.1%), and Asians (64.4%, 23.6%, 11.9%). As demonstrated in Table 1, compared to Whites, regardless of stage, survival was worse for Blacks (HR 1.16) and Asians (HR 1.14). As expected, survival was inferior for pts with sarcomatoid MMP followed by biphasic. Epithelioid MMP had the most favorable prognosis. Lastly, using the CDC WONDER database over the same period, there were 47,323 White, 2,068 Black, and 541 Asian MMP deaths. AAM was 0.8, 0.3, and 0.2 per 100,000 persons for White, Black, and Asian patients, respectively. AAM declined from 2000 to 2019 by 22% (0.9 to 0.7) in White, 50% (0.4 to 0.2) in Black, and 33% (0.3 to 0.2) in Asian. Conclusions: This is one of the largest population-based studies analyzing MMP racial disparities and histologic subtypes. Mortality analysis revealed declines across all racial groups, with the greatest decline among Blacks, which is two-fold that of Whites. However, a survival gap between races and histological subtypes persists. Despite no differences in the prevalence of histologic subtypes, mortality was 16% higher for Black patients when compared to Whites. Asian patients also had a higher risk of death of 14%, though the aggressive sarcomatoid subtype was more prevalent in this racial group. Social determinants of health and biological differences, could be responsible. Further studies are needed. [Table: see text]
Survival trends among patients with mesothelioma: Impact of initial therapy at academic centers.
Authors: Mooradian Ariana , Kimbrough ErinMarie , Hochwald Alexander , Sacchi de Camargo Correia Guilherme , Manochakian Rami , Zhao Yujie , Lou Yanyan
Published: June 2023

e20540

Background: Mesothelioma is an aggressive malignancy with few approved treatment options. Rare malignancies are often seen in higher volume at academic centers which are considered equipped with better expertise. Outcomes of mesothelioma in the novel therapeutic era and impact of initial treatment at academic versus community centers have not been reported. Methods: Mesothelioma cases from 2004-2019 were collected from The National Cancer Database (NCDB). Epidemiologic factors including sex, age, income, education, insurance status and location were assessed as well as overall survival across academic and community centers. Overall survival (OS) was plotted by type of treatment facility, accounting for several factors available in NCDB. Results: A total of 30136 mesothelioma patients were included in the analysis. 13482 (44.7%) were treated in academic centers and 16654 (55.3%) were treated in community practice locations. A higher proportion of patients with comorbidity scores of 2 or higher were seen in the community setting as compared to the academic setting (12.2% vs 7.6%). The distribution of diagnostic stages was similar between academic and community settings (14.1% vs 14.5% Stage I; 28.5% vs 30.7% Stage IV). A higher number of patients received surgery (39.6% vs 21.3%), chemotherapy (59% vs 45.3%), and immunotherapy (5.2% vs 3.5%) when presenting to academic rather than community settings, respectively (p value < 0.001). OS for all patients was 1.093 years (range: 0-16.47 years) for those treated in an academic center and 0.66 years (95% CI: 0-16.690; p < 0.001) for those treated in the community. Conclusions: Data from NCDB database shows that treatment of mesothelioma at academic centers was associated with improved overall survival when compared to receiving treatment in the community despite seeing similar proportions of early and late-stage disease at presentation. Patients were more likely to receive treatment of any kind if presenting to academic centers.
Incidence of immune checkpoint inhibitor induced myocarditis in patients with mesothelioma from a regional tertiary cancer centre covering a patient population of 2.6 million.
Authors: Johnson Alexandra , Chapman Adam , Garbutt Nicholas , Griffiths Richard , Pope Anthony , Olsson-Brown Anna Claire
Published: June 2023

e20541

Background: As a large regional tertiary cancer centre with an established cardio-oncology service a high incidence immune checkpoint inhibitor (ICI) induced myocarditis was recognised in mesothelioma patients receiving combination ICIs (cICI). A retrospective analysis of myocarditis in patients with mesothelioma was conducted. The utility of baseline cardiac markers as a prospective stratification tool for the development of ICI induced myocarditis in this patient group was investigated. Methods: A retrospective analysis of 118 patients with mesothelioma treated with ICIs over a 5 year period at the Clatterbridge Cancer Centre, Liverpool, UK. Baseline characteristics, treatment regimen, co-morbidities and the presence of malignant pericardial or cardiac disease were recorded. Baseline cardiac markers (high sensitivity Troponin T (hsTT) and pro-BNP) were recorded for patients initiating ICI treatment from July 2022 when regional baseline testing was introduced. A diagnosis of myocarditis was confirmed by cardiac MRI (n = 6) or clinically by the cardio-oncology team when MRI was clinically unfeasible (n = 1). Statistical analysis was undertaken with Fishers Exact test. Results: 33 patients received cICI treatment with Ipilimumab and Nivolumab, 85 patients received monotherapy ICIs (mICI), 5 as a SACT combination. Myocarditis occurred in 12.1% (n = 4) of patients receiving cICIs vs 3.5% (n = 3) of patients receiving mICIs. The median onset was 57 days with cICI and 245 days with mICI treatment. Baseline (b/l) cardiac assessment was undertaken in 22 patients (66.7%) of those treated with cICIs and 8 patients (9.4%) treated with mICI therapy. An abnormal b/l pro-BNP ( > 500 ng/L) was identified in 5 cICI patients and 1 mICI patient. Those with elevated b/l pro-BNP in the cICI setting all had a significant cardiac association; either an increased incidence of myocarditis (n = 3/5) (p = 0.0065) or pericardial/ invasive cardiac disease (n = 2/5) (p = 0.0433). In the cICI population myocarditis was not seen in patients with a b/l pro-BNP < 500ng/L. Of the 8 mICI patients with b/l cardiac assessment, 1 patient had an elevated pro-BNP which was associated with pericardial extension. Regarding baseline hsTT in the cICI group, the incidence of myocarditis was not increased with mild b/l elevations (14-24 ng/L), however, a moderately elevated level ( > 24ng/L) was associated with an increased incidence of myocarditis (p = 0.0026). Conclusions: In this cohort of patients with mesothelioma there was a high incidence of cICI induced myocarditis. As patients treated with cICIs with abnormal b/l cardiac markers had an increased risk of developing ICI induced myocarditis, b/l cardiac markers could potentially be used to help stratify the risk of ICI induced myocarditis and inform treatment discussions. Further studies are now required.
Demographic and racial characteristics, and survival trends in pleural mesothelioma: A population based study.
Authors: Patel Dhaval , Yadukumar Lekha , Dourado Claudia M. , Leighton John Charles
Published: June 2023

e20543

Background: Mesothelioma is a rare and aggressive type of cancer that originates from the visceral and parietal pleura. Approximately 3,000 people are diagnosed with mesothelioma in the United States each year ( < 0.03% of all cancers). The prognosis is poor, with a 5-year survival rate of only 7 to 10%. With a latency period of 30 to 60 years, mesothelioma is typically diagnosed at an advanced age. Our objective is to investigate the demographic and racial factors that affect prognosis and survival rates in patients with pleural mesothelioma. Methods: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database. Socioeconomic and racial factors in 13,166 patients diagnosed with mesothelioma from 2000 to 2019 were analyzed using the Pearson chi-square test. Cancer-specific survival outcomes were compared across racial and ethnic factors using the Kaplan-Meier analysis. Results: The patients were predominantly male (78.3%) and White (91.3%). Gender-based differences were narrower among the Asian/Pacific Islander population (74.5% male vs. 25.5% female) and Black population (76.8% male vs. 23.2% female) compared to Whites (78.5% male vs. 21.5% female). In the Asian/Pacific Islander population, 59.7% of patients were diagnosed with mesothelioma after 2010, compared to 40.3% diagnosed before 2010 (p-value < 0.001). Of the 12,029 new mesothelioma diagnoses in the White population, 51.6% occurred before 2010 and 48.4% after 2010. Distant disease was more prevalent in the Black population at 68%, compared to 64% in White patients and 62.3% in Asian/Pacific Islanders. Patients with a household income above $65,000 accounted for 60.8%. 57.9% of Black patients had an income below $65,000, compared to 38.9% of White patients and 23% of Asian/Pacific Islanders. At diagnosis, 51% of Black patients were married, compared to 69.5% of Asian/Pacific Islander patients and 64.5% of White patients. Chemotherapy was administered to 41.7% of patients (p-value < 0.07), followed by surgery (24.5%, p-value < 0.003) and radiation (10.4%, p-value < 0.026). 75.8% of Black individuals did not receive treatment, compared to 71.6% of Asian/Pacific Islanders and 70.1% of White patients (p-value < 0.001). The cumulative incidence of mesothelioma-related death was 70.2%. The 1-year, 3-year, and 5-year survival rates for Black patients were 29%, 5%, and 1% respectively; for White patients, the rates were 33.2%, 6.5%, and 2.1%; and for Asian/Pacific Islander patients, the rates were 31%, 6%, and 2%. Conclusions: Our study highlights the interplay of socioeconomic and racial factors that may impact survival trends. Black patients have a poorer survival rate compared to White and Asian/Pacific Islander populations. This disparity could be attributed to several factors such as later stage diagnosis, lower marital status, household income, and reduced access to treatment options.
Respiratory toxicities after concurrent chemoradiotherapy and subsequent consolidation immune checkpoint inhibitors in locally advanced non-small cell lung cancer: Infectious and non-infectious subtypes by pathogen NGS testing.
Authors: Qiu Bo , Xiong Mai , Liu FangJie , Zhang PengXin , Zhou Rui , Wang DaQuan , Luo YiFeng , Liu YiMei , Guo JinYu , Chen NaiBin , Li Shiyue , Liu Hui
Published: June 2023

e20557

Background: Consolidation immune checkpoint inhibitors (ICIs) following concurrent chemoradiotherapy (CCRT) have significantly improved survival in locally advanced non-small cell lung cancer (LA-NSCLC), while the associated respiratory toxicities were of particular concern. We aimed to investigate the > = G2 respiratory toxicities, the characteristics of concomitant infection, and provide detailed information for clinical management. Methods: We reviewed 77 LA-NSCLC patients treated with CCRT and consolidation ICIs. The details of > = G2 respiratory toxicities and concomitant infection were analyzed. Potential risk factors for > = G2 respiratory toxicities were explored by univariable and multivariable analysis. Respiratory toxicities were collected from the start of consolidation ICIs till 6 months after the last infusion of ICIs. Concomitant infection was defined as positive findings from next-generation sequencing (NGS) of bronchoalveolar lavage sampling. Results: Patients were treated with definitive radiotherapy at a median dose of 60 Gy (IQR, 60-64), concurrently with weekly docetaxel and platinum and followed by single-agent ICIs. The median duration of consolidation ICIs was 5.4 months (IQR, 2.3-8.2). Twenty-six patients (33.8%) experienced > = G2 respiratory toxicities by a median of 4.8 months (IQR 1.5-6.6) after initiation of consolidation ICIs. Pneumonitis (14, 18.2%) and tracheobronchitis (13, 16.9%) were the most common > = G2 respiratory disorders. Location of primary tumor (p = 0.027) and the proportion of CD3+ lymphocyte before consolidation ICIs (p = 0.044) were independent risk factors for the occurrence of > = G2 respiratory toxicities. Eleven patients (14.3%) had > = G2 respiratory toxicities and concomitant infection. Identified pathogens included bacteria (n = 9), Aspergillus (n = 5), Pneumocystis (n = 1) and Leptosvirus (n = 1). Concomitant infection was more commonly detected in patients with tracheobronchitis compared with those with pneumonitis ( p= 0.002), was associated with a higher grade of toxicity ( p= 0.050) and relatively poorer outcome after management ( p= 0.002). Conclusions: Respiratory toxicities after CCRT and subsequent consolidation ICIs in LA-NSCLC mainly included pneumonitis and tracheobronchitis, and could be separated into infectious and non-infectious subtypes. Bacteria and Aspergillus were the predominant pathogens. Our findings highlight the importance of the bronchoscopy and pathogen NGS testing to detect airway disease and specific infection. Long-term systemic steroids might adversely affect respiratory toxicities with concomitant opportunistic infection, which should be taken into account at the onset of management.
The association between body mass index and distribution intensity of tumor treating fields (TTFields) in the lungs.
Authors: Mooney Carly , Naveh Ariel , Shapira Nadav , Berger Brian
Published: June 2023

e20559

Background: Tumor Treating Fields (TTFields) therapy is a first-in-class locoregional and noninvasive cancer treatment modality. TTFields are electric fields that disrupt processes necessary for cancer cell viability and tumor progression. A portable medical device generates TTFields, which are delivered noninvasively to the tumor area via 2 pairs of transducer arrays placed on the skin. TTFields therapy is currently approved for recurrent and newly diagnosed glioblastoma and pleural mesothelioma, with studies underway in other solid tumor types, including non-small cell lung cancer (NSCLC). Preclinical studies have shown that the effectiveness of TTFields depends on several factors, including field intensity. Given that 1 in 3 adults is overweight or obese, it is relevant to determine the effect of body mass index (BMI) on TTFields intensity to the lungs. Simulation-based methods were utilized, with the hypothesis that TTFields could be delivered to regions of interest (ROI) at therapeutic field intensities of > 1 V/cm, irrespective of BMI. Methods: Female computer phantom models with BMIs of 22 (healthy), 26 (overweight), and 30 (obese) were used to simulate TTFields intensity using small (13 disk) and large (20 disk) arrays placed on the thoracic region. The distribution of TTFields in each model was then determined using a computer-generated electric field intensity map. Field intensity values across the entire lungs were analyzed and compared. Results: When TTFields were delivered with large arrays, field intensities were clinically meaningful ( > 1 V/cm) in all lobes of the lungs for all BMI models. When TTFields were delivered with small arrays, meaningful levels of field intensity were achieved in all lung lobes, except for the BMI 30 model, where field intensities were slightly lower than 1 V/cm in the right middle lobe. Conclusions: These results show that TTFields can be delivered at therapeutic field intensities in patients with a BMI up to 30, providing the appropriate TTFields array size is used. Results from this simulation-based study support current clinical studies of TTFields therapy in lung cancer, (LUNAR, NCT02973789) and underscore the importance of appropriate array size selection. Additionally, these results may provide guidance for using TTFields therapy to treat a broad population of patients with lung tumors.
Endostatin in combination with PD-1 antibody plus chemotherapy as first-line regimen for EGFR/ALK-negative, advanced or metastatic non-small cell lung cancer: A real-world study.
Authors: Zhang Jing , Sun Shengjie , Zhao Xiao , Liu Minglu , Qiu Lupeng , Yang Zizhong , Zhang Guoqing
Published: June 2023

e20564

Background: In recent years, treatment for advanced or metastatic NSCLC has been significantly improved with the emergence of a combination strategy of immunotherapy with antiangiogenic drugs plus chemotherapy. Although endostatin (an antiangiogenic agent) combined with chemotherapy has been approved by the China Food and Drug Administration in treatment-naïve and re-treatment NSCLC patients, the clinical evidence supporting its combination with programmed cell death-1 (PD-1) antibody for advanced or metastatic NSCLC is still insufficient. Therefore, we aimed to evaluate the effectiveness and safety of endostatin combined with PD-1 antibody plus chemotherapy as the first-line treatment for locally advanced or distant metastatic NSCLC with EGFR/ALK-negative. Methods: This was a retrospective, singer-center, real-world study conducted between June 2018 and December 2021. The primary endpoint was progression-free survival (PFS); the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: Overall, 68 patients were included. The median PFS and OS were 22.0 months (95% confidence interval [CI]: 16.6-27.4 months) and 31.0 months (95% CI: 23.4 months-not reached [NR]), respectively, with a median follow-up of 21.4 months (range, 8.3-44.4 months). At the data cutoff, 33 patients (48.5%) remained progression-free and 24 patients (35.3%) had died. Short-term clinical efficacy was assessed after 2 consecutive treatment cycles, with an ORR of 72.06% (complete response [CR], n = 3; partial response [PR], n = 46) and a DCR of 95.59% (CR, n = 3; PR, n = 46; stable disease, n = 16). Further subgroup analysis determined that a significantly better ORR (89.2% vs. 51.6%), median PFS (23.4 vs. 13.2 months), and median OS (NR vs. 18.0 months) for patients with stage Ⅲ B/Ⅲ C vs. stage Ⅳ NSCLC (all p ≤ 0.001). Besides, the median PFS (8.0 months vs. 22.5 months, p = 0.004) and OS (13.0 vs. 31.0 months, p = 0.027) of patients with brain metastasis were significantly shorter than those without brain metastasis. The ORR in patients who had a PD-L1 tumor proportion score (TPS) of < 1%, 1%-49%, ≥ 50%, and unknown were 50%, 50%, 75.0%, and 86.1%, respectively ( p = 0.025). All patients (100%) experienced treatment-related adverse events (AEs). The majority of AEs were grade 1 or 2 (57/68, 83.82%). Conclusions: In the real-world scenario, endostatin combination with PD-1 antibody plus chemotherapy obtained encouraging efficacy and favorable safety in advanced or metastatic NSCLC. The combination strategy in this study furnished beneficial evidence for the treatment of advanced or metastatic NSCLC and is essential for determining the best treatment option.
A preliminary analysis of integrating thymosin α1 into concurrent chemoradiotherapy and consolidative immunotherapy.
Authors: Liu FangJie , Qiu Bo , Wang DaQuan , Zhou Rui , Zhang PengXin , Zheng ShiYang , Guo JinYu , Luo QiaoTing , Guo SuPing , Liu Hui
Published: June 2023

e20569

Background: The study aimed to investigate the efficacy of integrating Thymosin into concurrent chemoradiotherapy (CCRT) and consolidative immunotherapy in unresectable locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Ninety-one stage IIIA-IIIC LA-NSCLC patients enrolled from Jan 1, 2020, to Oct 31, 2022 were analyzed retrospectively. All patients received CCRT (total irradiation dose of 60Gy and weekly concurrent docetaxel and cisplatin) and consolidative immunotherapy (Nivolumab/Tislelizumab). Thymosin α1 (1.6 mg) was administered once a week from the start of treatment till 2 months after CCRT or till the last prescription of consolidative immunotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included the overall survival (OS) and toxicity. Results: There were 31 patients who received Thymosin α1 till the last prescription of consolidative immunotherapy, 40 patients received Thymosin α1 till 2 months after CCRT and 20 patients without the administration of Thymosin α1. The median follow-up time was 28.3 months (range 8.2~31.6 months). The median PFS was 26.1 months in Thymosin α1+consolidative immunotherapy group, 15.3 months in Thymosin α1+CCRT group and 12.6 months in control group (P = 0.116). The median OS was not reached in Thymosin α1+consolidative immunotherapy group, 26 months in Thymosin α1+CCRT group and 16.5 months in control group (P = 0.046). The median courses of consolidative immunotherapy were 8 Thymosin α1+consolidative immunotherapy group, 6 in Thymosin α1+CCRT group and 3 in control group (P = 0.060). There were higher ≥grade 3 acute lymphopenia (62.3%) and acute grade 2 pneumonitis (8.0%) in the control group. The long-term use of Thymosin α1 was also found to be related to the lower level of IL-6(P = 0.048), CD 16+NK cells and CD56+NK cells (P = 0.043). Conclusions: The integration of Thymosin α1 into CCRT and consolidative immunotherapy could yield synergistic effect in LA-NSCLC patients. The combination might contribute to prolonged use of consolidative immunotherapy and survival benefit.
Impact of SARS-COV2 infection on the clinical outcomes in patients with lung cancer.
Authors: Swarna Siri Chandana , Deenadayalan Vaishali , Litvin Rafaella , Dasgupta Mona , Kim Junglee , Gupta Shweta
Published: June 2023

e20572

Background: The outbreak of 2019 Novel coronavirus disease (COVID-19) has led to various deleterious outcomes in cancer patients. Those with lung cancer would be more susceptible to increased morbidity and mortality. We aimed to study the outcomes of COVID infection in patients with lung cancer. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database-2020 was queried to identify all admissions with COVID in patients with and without lung cancer. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included a diagnosis of thrombocytopenia (TCP), Acute Respiratory Failure (ARF), sepsis, anemia, pancytopenia and shock. Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total 4,625 COVID admissions occurred in patients with lung cancer. Among them 71% (N = 3,288) were white, 17% (N = 805) were African American (AA) and 6.7% (N = 310) were Hispanic (HISP). Lung cancer patients had higher rates of smoking heart failure, CKD, CAD, COPD and anemia (p < 0.01) and lower rates of DM and obesity (p < 0.01). Lung cancer patients were more likely to have Medicare and less likely to have private insurance and were older (mean age 64.7 vs 71.9, p < 0.01). On multivariate regression, after adjusting for confounders those with lung cancer had higher odds of all-cause mortality (aOR 1.41; 95% CI 1.18-1.70 ,p = < 0.001). Among lung cancer patients, mean LOS was lower by 1 day (95% CI -1.4 to -0.4, p < 0.001) and THC was also lower (-$16,672; 95% CI -22950 to -10393, p < 0.001). Among the secondary outcomes, lung cancer patients had higher rates of pancytopenia (7.46% vs 1.59%, p < 0.001), neutropenia (3.46% vs 0.68%, p < 0.001) and venous thromboembolism (8.97% vs 4.29%, p = 0.006). Conclusions: COVID-19 infection led to increased mortality in lung cancer patients compared to those without lung cancer. This explains the overwhelming impact the pandemic left on lung cancer patients. The LOS and THC was decreased for lung cancer patients which may be explained by early death compared to non-lung cancer cohort. This study highlights the importance of decreasing the risk factors for COVID infection among lung cancer patients, including encouraging vaccination.
Deep learning algorithm for automatic prediction of visceral pleural invasion of lung cancer based on surgical video.
Authors: Xu Hao , Mu Wei , Zou Ruiyang , Cao Caifang , Sun Zewen , Cheng Sida , Guan Tian , Li Hao , Chen Xiuyuan , Jiang Guanchao , Yang Fan , Wang Jun , Tian Jie , Zhou Jian
Published: June 2023

e20578

Background: Visceral pleural invasion (VPI) is an important prognostic indicator in lung cancer that is difficult to predict. We aimed to develop a deep learning algorithm that predicts VPI using videos of lesions. Methods: We included 346 patients who underwent thoracoscopic surgery at our department from 2015 to 2021, corresponding to 3800 images. The patient data and image data were divided into training set, validation set and testing set. The algorithm was developed based on the ResNet architecture used for image feature extraction and classification. All images were labeled for lesions and processed to fit the algorithm. We recruited two thoracic attendings and one radiologist to identify VPI using intraoperative video and preoperative CT, respectively. The performance of the algorithm was evaluated by comparison with the performance of the attendings and the radiologist. Results: At the patient level, the algorithm had satisfactory AUC values in the training set (0.85), validation set (0.83) and testing set (0.81). The DeLong test showed statistic difference between the algorithm and two attendings and a radiologist in the training set (p < 0.001, p < 0.001, p < 0.001), validation set ( p= 0.006, p= 0.002, p= 0.026) and testing set ( p= 0.008, p= 0.012, p= 0.007). At the image level, the algorithm also outperformed two attendings and a radiologist with significantly great AUC values in the training set (0.83 vs. 0.52 vs. 0.53 vs. 0.65; p< 0.001, p< 0.001, p< 0.001), validation set (0.78 vs. 0.50 vs. 0.54. vs. 0.68; p< 0.001, p< 0.001, p= 0.048) and testing set (0.79 vs. 0.53 vs. 0.60 vs. 0.58; p< 0.001, p< 0.001, p< 0.001). Conclusions: The video-based deep learning algorithm could satisfactorily predict VPI and achieved expert-level performance better than thoracic attending surgeons and the radiologist we recruited.
A 9-gene signature in circulating tumor DNA based on molecular residual disease detection to predict recurrence of resectable non–small-cell lung cancer.
Authors: Lu Di , Wang Zhouyu , Yang Airong , Chen Zhiming , Wang Zhizhi , Li Jing , Li Shaobin , Cai Kaican
Published: June 2023

e20579

Background: Molecular residual disease (MRD) status is associated with the recurrence of non-small cell lung cancer (NSCLC) after complete resection. In clinical practice, MRD-positive patients are still uncertain of the specific recurrence time, and may even not relapse. Besides, it remains unclear whether the mutational signatures of circulating tumor DNA (ctDNA) based on MRD detection (ctDNA-MRD) may help predict recurrence. Therefore, we performed this analysis to explore whether the ctDNA-MRD mutational signatures could help predict recurrence, especially in MRD-positive population. Methods: Two investigators independently searched public databases for articles related with MRD in lung cancer published up to July 31, 2022. After screening, raw data from two published studies on resectable NSCLC were analyzed. Gene clusters were established based on the clearance of ctDNA after surgery. Kaplan-Meier and multivariate analyses were performed to find genes (Monitor genes) and clinical variables associated with recurrence-free survival (RFS). Lasso method was used to find recurrence-related genes based on perioperative ctDNA (preoperative and longitudinal ctDNA). Monitor genes and recurrence-related genes were defined as 9-gene signature. The mutational status of Monitor genes and 9-gene signature in perioperative ctDNA, as well as clinical variables, were used to establish prognostic models. The power of the models in distinguishing recurrence was shown as the area under the curve (AUC). Results: Data from 168 patients with at least one somatic mutation detected in tumors were included in the analysis. DNMT3A, EGFR, TP53, KEAP1, NAV3 (Monitor genes), and clinical variables (stage, adjuvant therapy) were factors associated with RFS. The AUC of the model based on Monitor gene mutations in perioperative ctDNA was 0.774, and the AUC reached 0.807 when clinical variables were included. The AUC of the models based on clinical variables, 9-gene signature (Monitor genes, KRAS, NTRK3, RPL5, and SOX2) in perioperative ctDNA for predicting the recurrence in the overall population and MRD-positive population were 0.840 and 0.832, respectively. Conclusions: This analysis reveals that perioperative ctDNA mutational signatures are helpful to predict postoperative recurrence, so it is necessary to pay attention to the specific gene mutations in ctDNA-MRD. [Table: see text]
Multi-omics analysis to reveal the change of peripheral blood TCR repertoire and tumor burden during neoadjuvant chemotherapy combined with sequential PD-1 blockade for patients with non-small cell lung cancers: A single-center, single-arm phase 2 trial.
Authors: Yang Bo , Liang Chaoyang , Song Qi , Xiong Qi , Li Jie , Long Yaping , Zhou Wenhao
Published: June 2023

e20582

Background: Preoperative neoadjuvant chemotherapy combined with immunotherapy has been applied to the treatment of non-small cell lung cancer (NSCLC). However, the optimal dosage of chemotherapy and sequencing for chemotherapy and immunotherapy remains controversial. Methods: In this single-arm phase 2 trial, patients with stage IB to IIIA resectable NSCLC were enrolled and received 2 cycles of dose-limiting platinum-based chemotherapy (albumin-bound paclitaxel or pemetrexed plus cisplatin or carboplatin) on day 1, combined with sintilimab (200mg) on day 5 before undergoing radical surgery. Combination postoperative adjuvant therapy with the same regimen was administered. The primary endpoints were objective response rate (ORR) and major pathological response (MPR). Biopsies and plasma at different timepoint were collected and performed with RNA sequencing, circulating tumor DNA sequencing and T cell receptor (TCR) sequencing. Results: 17 patients were enrolled. After neoadjuvant treatment, patients with completed response, partial responses and stable diseases were 11.8% (2/17), 70.6% (12/17) and 17.6% (3/17), respectively, yielding an ORR of 82.4%. Radiological downstaging was achieved in 82.4% (14/17) of patients. All patients (17/17, 100%) experienced the R0 resection. Pathologic complete response and MPR were identified in 35.2% (6/17) patients and 23.5% (4/17) patients, respectively. Only 1 of the 17 patients (5.9%) experienced grade 3 or greater adverse event. Multi-omics analysis revealed chemotherapy combined with sequential PD-1 blockade results in the increase of dominated TCR clones and the decrease of the tumor burden. Especially during chemotherapy of cycle 1, the dominated TCR clones were significantly increased, and the maxVAF of ctDNA was significantly decreased. The change between the dominated TCR clones and maxVAF of ctDNA was negatively correlated. Conclusions: In patients with stage IB to IIIA resectable NSCLC, the neoadjuvant therapy with dose-limiting platinum-based chemotherapy combined with sequential sintilimab was safer and resulted in significant antitumor activity in patients with resectable NSCLC. The changes in TCR repertoire and ctDNA during treatment were analyzed, which provided evidence for the rationality of neoadjuvant chemotherapy combined with sequential PD-1 blockade. Clinical trial information: ChiCTR2000033092 .
NK cell expansion after primary multimodal treatment to predict progression free survival in inoperable stage III NSCLC.
Authors: Hofer Thomas Philipp , Käsmann Lukas , Nieto Alexander , Pelikan Carolyn , Taugner Julian , Eze Chukwuka , Tufman Amanda , Belka Claus , Manapov Farkhad , Noessner Elfriede
Published: June 2023

e20584

Background: During multimodal cancer therapy an acute lymphocytopenia occurs, which is associated with poor survival in inoperable stage III NSCLC patients. A prospective analysis of peripheral blood mononuclear cells (PBMCs) during multimodal treatment was performed to assess dynamic changes of leukocyte subpopulations after concurrent chemo-radioimmunotherapy (cCRT) in order to extract biomarkers to predict progression free survival (PFS). Methods: 20 patients (17 male, 3 female), at median age of 65.5 years (range 34 to 79), 11 suffering from adenocarcinoma, 8 squamous cell carcinoma, and 1 undifferentiated NSCLC, were enrolled in the study. They received thoracic radiotherapy (TRT, 2/20, 10%), cCRT (11/20, 55%), or cCRT with checkpoint inhibition (cCRT-ICI, 7/20, 35%), one patient (1/20, 5%) withdrew consent and was excluded from analysis. Patients were grouped into poor ( < 6months), intermediate (≥6 < 12 months), or favorable (≥12 months) PFS. Blood was analyzed via flow cytometry for leukocyte sub-populations at 9 time points. Here, we report on NK cells and focus on the time period starting after end of TRT until 6 months thereafter. The area under curve (AUC) of absolute cell counts for this period was calculated to provide an aggregate measure for the time-course dynamics. Results: NK cell counts were consistently low in all patients at the end of TRT. Patient-individual recovery of cell counts 6 months after RTend (expressed as the AUC) was observed, which was beneficially affected by consolidation ICI (one-tailed t-test, p = 0.031). Retrospective assignment of the AUC values to the PFS groups revealed a positive association of high AUC values with PFS. Patients with longest PFS (≥12 months; 9/19) had higher AUC values compared to patients with intermediate PFS (≥6 < 12 months; 5/19; t-test p = 0.043) or poor PFS ( < 6months; 5/19; p = 0.0018). The difference between AUC values of intermediate and poor PFS groups was also significant (p = 0.039). Conclusions: Patients who responded with early NK cell expansion after TRT, cCRT, or cCRT-ICI had significantly longer PFS compared to those without increase. Longitudinal monitoring of NK cells and calculating the AUC (RTend and 6 months thereafter), which reflects absolute cell counts, is a promising biomarker to predict PFS.
Characteristics of lung cancer in renal transplant recipients.
Authors: Sridhar Arthi , Yohannan Binoy , Kaur Harmanpreet
Published: June 2023

e20592

Background: Renal transplant recipients (RTRs) are at a higher risk of developing malignancies primarily due to prolonged immunosuppression. Lung cancer while rare in RTR, is associated with significant morbidity and mortality. The primary objective of our study is to analyze the clinical characteristics and outcomes of RTRs who developed lung cancer at our institution. Methods: We retrospectively reviewed 1998 RTRs who underwent transplantation between January 1, 1999, and December 31, 2019, at our institution and identified patients who were diagnosed with lung cancer after transplant. Baseline demographic variables and information related to the renal transplant, the diagnosis and management of lung cancer were collected. Results: Among 1998 RTRs, 10 patients (0.005%) developed lung cancer. A majority of the lung cancer patients identified as male (n = 8), and the median age was 62.5 years. The races of the patients were white (30%, n = 3), African American (50%, n = 5), Hispanic (10%, n = 1), and Native American (10%, n = 1). Concomitant liver transplant was performed in 2 patients, and a concomitant heart transplant was performed in 1 patient. Median time to lung cancer diagnosis after transplant was 67.5 months (range, 12-168). The histology of the lung cancers found were adenocarcinoma (n = 4), squamous (n = 4), and small cell (n = 2). All patients had a history of smoking, with 90% reporting a > 15 pack-year history of smoking and none of them received lung cancer screening. Among the patients with non-small cell lung cancer (NSCLC), 87.5% (n = 7) had early-stage disease, and 12.5% (n = 1) had locally advanced disease (Stage IIIB). Both patients diagnosed with small cell lung cancer had extensive-stage (es-SCLC) disease at the time of diagnosis. Among patients with NSCLC, 2 had genomic tumor profiling performed. Among patients with early-stage NSCLC, 57% underwent upfront surgery, 14% received radiation alone, 14% received neoadjuvant chemotherapy, and 14% received adjuvant chemotherapy. Around 71% (n = 5) remained alive at the last follow up recorded. The patient with stage IIIB NSCLC received chemotherapy and concomitant radiation but had an overall survival (OS) of only 6 months; that patient died of complications related to cancer progression. Both patients with es-SCLC received front-line chemotherapy with carboplatin and etoposide. To our knowledge, 40% (n = 4) of these patients retained their renal graft function. At 1-year from diagnosis, 40% of patients diagnosed with lung cancer were still alive. Conclusions: Lung cancer in RTRs is rare but is associated with significant morbidity and mortality. With the improving life expectancy of RTRs, the incidence of de novo malignancies including lung cancer is likely to increase. Annual screening for lung cancer in high-risk individuals is an important step for early diagnosis. Surgical resection and chemotherapy are well tolerated in patients with lung cancer.
Establishment of a nomogram predictive model for survival and prognosis of 97 patients with different subtypes of lung adenocarcinoma after radical resection.
Authors: Aosiman Aliya , Aerxiding Patiguli , Nuermaimaiti Gulinuer , Zheng Yang , Meng Yuan
Published: June 2023

e20596

Background: Postoperative recurrence and metastasis of lung adenocarcinoma (LUAD) is a major obstacle to long-term survival, and how to identify patients at high risk of recurrence / death after surgery and those likely to benefit from adjuvant therapy is currently a clinically relevant question. In this study, we investigated the survival characteristics of patients with different subtypes of LUAD after radical resection and established predictive prognostic models to inform postoperative management, recurrence prediction and risk management in lung cancer patients. Methods: A retrospective analysis of 97 patients who underwent concurrent genetic testing for LUAD radical resection at The Affiliated Tumor Hospital of Xinjiang Medical University between December 01, 2014 and December 30, 2017 was performed. A COX proportional risk regression model was used to construct a prognosis model for patients with LUAD after surgery and visualization of the model was performed using column diagrams. The performance of the model was evaluated using C index, calibration curve, and ROC curve. Results: (1)46 patients (47.42%) were included and 51 patients died (52.58%), with a median survival of 78 months (95% CI: 63-93). Twenty of these patients had a good prognosis (20.62%) and 77 had a poor prognosis (79.38%), with a median survival time of 88 months (95% CI: 81-95). The overall survival rate was 98.9%, 78.3% and 59.7%, respectively, and the cumulative disease-free survival rate was 77.3%, 37.1% and 20.6%, respectively, for 1, 3 and 5 years. Pathologic types were lepidic, acina/papillaryand solid/micropapillary with 87.50%, 56.90% and 58.80% OS and DFS, respectively. 37.50%、80%、11.80%. (2)26 patients (26.8%)had recurrent metastasis,the main site of metastasis was extrapulmonary, and multiple metastases were more common. (3)Univariateand multivariate analysis showed that TNM stage III, pathological classification as solid/micropapillary, tumor diameter ≥ 3cm, and gene mutation positivity were independent risk factors for prognosis in patients with lung adenocarcinoma after surgery. Based on the above risk factors, the Nomogram prognostic model was established with a C index of 0.687 (95% CI: 0.622-0.752) and calibration curves and ROCs for the 1, 3, and 5 year models, respectively, with AUC values of 0.742, 0.752, and 0.820 > 0.7, suggesting that the model is within the acceptable range of partitioning and accuracy, with the highest AUC for the 5-year DFS prediction. Conclusions: High TNM staging, pathotyping of micronipples or entities, ≥ 3cm tumor diameter, and mutant positivity were independent risk factors for recurrence and metastasis in patients with LUAD. The Nomogram predictive model based on patient risk factors after LUAD radical resection is effective in predicting long-term survival and guiding personalized treatment.
Comprehensive genetic characteristics of multiple primary lung cancer in patients in China.
Authors: Pei Guotian , Yang Yingshun , Li Mingwei , Ma Xiaoxue , Qin Jiayue , Cao Shanbo , Liu Qiang , Wang Shuai , Huang Yuqing
Published: June 2023

e20597

Background: With the development of molecular biology and next-generation sequencing (NGS), researchers have been exploring the use of genomic technologies for the classification of lung cancers. The aim of this study was to investigate genetic characteristics of multiple primary lung cancer (MPLC) to facilitate precise diagnosis and therapy by NGS. Methods: A total of 271 lesions from 92 patients with MPLC (225 lesions) and 20 intrapulmonary metastasis (IM, 46 lesions) which were diagnosed by American College of Chest Physicians (ACCP) guidelines, were sequenced by Acornmed panel with 808 cancer-related genes. Results: The most frequent mutation in 225 lesions was EGFR (46.7%), followed by RBM10 (19.6%), BRAF (16.4%) and KRAS (15.1%) among MPLC while IM lesions showed high TP53 (63.0%) mutation frequency. Further analysis showed that MPLC patients had higher proportion of private mutations, and lower proportion of shared mutations and branch shared mutations than IM (p < 0.0001). In our cohort, 95.7% (88/92) of MPLC patients had at least one driver alteration, and EGFR and KRAS comprised 57.4% and 18.0% of 183 driver mutations, respectively. Further analysis showed that only 19.6% (18/92) of MPLC shared the same driver mutation in each patient and 61.1% (11/18) of co-driver mutation was EGFR L858R which was commonly detected in lung cancer. In contrast, 95.0% (19/20) of IM shared the same driver mutation in each patient. MPLCs were associated with a high frequency of T > C transitions (p < 0.001), while T > G transversions (p < 0.001) were more frequent in tumors from IM. MPLC had significantly higher intratumor heterogeneity (ITH) (17.1 vs 4.05, p < 0.001) and lower weighted-genomic integrity index (wGII) than IM (0.01638 vs 0.18321, p < 0.001). Besides, MPLC had lower percentage of clonal mutations (p < 0.001) than IM. However, IM had higher arm-level somatic copy number variations fraction (p < 0.001) than MPLC. Conclusions: Our analysis reveals that patients with MPLC have distinct molecular characteristics different from IM, which may increase the understanding of MPLC. In addition, the molecular features of MPLC may provide new opportunities to distinguish MPLC from IM by broad panel NGS.
CT based radiomics signature for phenotyping histopathological subtype in patients with non-small cell lung cancer.
Authors: Liu Yan , Zerka Fadila , Bodard Sylvain , Felfli Mehdi , Voyton Charles , Thinnes Alexandre , Jacques Sebastien , Iannessi Antoine
Published: June 2023

e20599

Background: The determination of the histopathology of non-small cell lung cancer (NSCLC) is crucial for guiding the appropriate therapeutic strategy, affecting prognosis and recurrence rates. In addition, targetable oncologic mutations are highly correlated to histological subtypes. Conventional methods such as biopsy or surgical excision are the primary methods for histology determination but are invasive, costly, and have limitations such as sampling error. Computed tomography (CT) scans, widely used for NSCLC diagnosis and follow-up, offer a non-invasive alternative through radiomics-based models that provide comprehensive analysis of the entire tumor and surrounding tissue, improving patient selection and stratification in clinical trials and enhancing the development of molecularly targeted drugs. The goal of this study was to evaluate the ability of a CT-based radiomics model to predict the subtype histopathology of NSCLC patients. Methods: A total of 678 patients with advanced-stage NSCLC with at least one measurable lung lesion (≥10mm) were selected from multicenter institutions; 531 were used for training and 147 for independent testing. The test set originates from centers unique from the training cohort. Semi-automatic segmentation of the lung lesions was performed and the segmentations were retrospectively reviewed by an experienced radiologist with > 20 years of experience. A total of 1246 radiomics features were extracted using the Pyradiomics package. Ten Robust features were selected first by removing all features with variances near zero, then by applying Maximum Relevance — Minimum Redundancy to the remaining features. All selected features were standardized before modeling. A support vector machines classifier was trained using a five-fold cross-validation and Random Over-Sampling Examples to classify the histology of NSCLC patients (Squamous vs. Non-Squamous). Results: The model trained with the radiomics features achieved a mean area under the curve (AUC) of 0.80 (95% CI, ±0.05) on the cross-validation and an AUC of 0.77 (95% CI, ±0.05) on the test set. Conclusions: Results showed that the model was able to accurately classify the histology of NSCLC patients as squamous vs. non-squamous in a multicenter setting. It highlights the promise of CT-based radiomics in determining the histopathology or other molecular biomarkers of NSCLC, offering a more efficient, cost-effective, and less invasive alternative to traditional tissue analysis methods. Our findings suggest that this non-invasive method has the potential to improve patient selection and stratification and enhance the development of molecularly targeted drugs. These results underscore the importance of incorporating advanced imaging techniques and machine learning algorithms into oncology practice for better patient outcomes.