tbuckley/cabot-search huggingface dataset:
Reducing the risk of grade 3 or greater radiation pneumonitis after radical radiotherapy to the lung.
Authors: Yujie Yan, Jingjing Kang, Shuangyan Yang, Cheng Qian, Ying Zhang, Xiaoshuai Yuan, Min Hu, Yaoyao Zhu, Chenxue Jiang, Minren Hu, Ruifeng Zhao, Lan Zhao, Xu Yaping
Journal: Journal of Clinical Oncology (2024)

e20008 Background: Radiation pneumonitis (RP) is the most common adverse response in patients with lung cancer receiving thoracic radiotherapy. Higher grade RP is more likely to lead to mortality and poor quality of life, which could be abated by rigorous treatment standards formulated with individualized clinical characteristics. In this study, we aimed to identify the best clinical prognostic model for evaluating patients with lung cancer after radical radiotherapy. Methods: We collected information of RP patients in recent years and established the new consensus on the diagnosis and treatment of radiation-related pneumonitis. In a nutshell, clinical data of patients treated with radical radiotherapy were collected from August 2020 to August 2022, and part of patients from August 2021 to August 2022 was been intervented by treatment methods. The interventions included limited irradiation of the planning target volume (PTV), individualized lung dose limitation, and standardized steroid therapy. Clinical characteristics including baseline and treatment data were obtained from 693 patients, including 623 patients in the training cohort and 70 patients in the test cohort. Three models were built using different screening methods, including multivariate logistics regression (MLR), backward stepwise regression (BSR), and random forest regression (RFR), to evaluate their prognostic power. Overoptimism in the training cohorts was evaluated by four validation methods including hold-out, 10-fold, leave-one-out, and bootstrap methods, and extra data were used to evaluate the predictive performance of the model. Model calibration, Decision curve analysis (DCA), and evaluation of the nomograms for the three models were completed. Results: The incidence of RP was significantly decreased after the interventions compared to before (68.80% vs. 59.56%, P &lt; 0.05), and the probability of grade 3 or higher RP also decreased from 11.97% to 6.67% (P &lt; 0.05). A model of intervention, interstitial lung disease (ILD), concurrent chemoradiotherapy, standardized steroids, carbon monoxide diffusing capacity (DLCO) &gt; 86.9%, and total lung volume exceeding 5 Gy (V5) &gt; 35.2% for the radiological parameter had the best discriminative ability with an area under the curve of 0.963 (95% CI: 0.938–0.989) in the training chort . The calibration curve showed good agreement between the predicted and actual values, and the DCA showed a positive net benefit for the final model based on the nomogram. Conclusions: The implementation of standardized interventions for the prevention and treatment of RP accompanied with standardized use of steroids resulted in a significant decrease in the incidence of grade 3 or higher RP. Early intervention and methods for reducing the complications of high-dose steroids will be explored in future work.
PM 2.5 and risk of lung cancer and associated mortality: An umbrella meta-analysis.
Authors: Ashima Gupta, Abhishek Singh, Baris Tarimci, Alamjeet Kaur Sindhu, Pinank Bathvar, Simranjeet Bedi, Nyein Wint Yee Theik, Vedant Shah, Saarthak Malhotra, Milan Khealani, Sri Usha Jeevani Obulareddy, Geetika Kukreja, Amaraja Kanitkar
Journal: Journal of Clinical Oncology (2024)

e20012 Background: PM 2.5, particulate matter with a diameter of 2.5 micrometers or less, is a major contributor to lung cancer and associated mortality. Epidemiological studies reveal a concerning trend, with each 10 micrograms per cubic meter increase in PM 2.5 associated with a 15% higher risk of lung cancer and a 13% increase in mortality rates, underscoring the significant burden it imposes on public health systems globally. We aimed to evaluate the odds of association between environmental exposure to PM 2.5 and the risk of lung cancer and associated mortality. Methods: We performed a systematic review and umbrella meta-analysis using studies containing quantitative data on PM 2.5 and lung cancer. We used PRISMA guidelines and the MOOSE protocol using PubMed and MeSH terms like PM 2.5, non-small cell cancer, lung cancer, pollutants, particulate matter 2.5, and environmental factors. We had excluded non-full-length articles, non-meta-analysis studies, and non-human studies. RavMan 5.4 was used, and generic inverse variance methods with mixed effect models were applied to identify a pooled risk ratio with a 95% confidence interval. Forest plots were obtained, and sensitivity analysis was performed based on funnel plots and I 2 (heterogeneity) values. Results: Of the 245,529 articles evaluated for the quality of the data, 99 met the inclusion and exclusion criteria. Out of 99, we used six articles to derive the quantitative data. In umbrella meta-analysis, PM 2.5 exposure was associated with a 1.16 times higher risk (95%CI: 1.1-1.22, p&lt;0.00001, I 2 =0%) of lung cancer and a 1.22 times higher risk of non-lung cancers (95%CI: 1.15-1.30, p&lt;0.00001, I 2 =0%). PM 2.5 was associated with non-significant higher mortality (RR: 1.06, 95%CI: 0.99-1.13, p=0.09, I 2 =97%) with leave-on-out analysis (excluding Chen et al.) significant association between mortality and PM 2.5 (RR: 1.08, 95%CI: 1.06-1.10, p&lt;0.00001, I 2 =0%). Conclusions: Our umbrella meta-analysis shows a significant risk of lung cancer and mortality from PM 2.5 exposure. Further investigation and increased consciousness are necessary to mitigate the risk of lung cancer associated with this pollutant.
Sex-based disparities in patients with lung cancer undergoing lobectomy via robotic-assisted thoracoscopic surgery.
Authors: Dhruvkumar Gadhiya, Saisree Reddy Adla Jala, Hemamalini Sakthivel, Kanwar Bir Singh Dhaliwal, Kamleshun Ramphul, Shivani Sharma
Journal: Journal of Clinical Oncology (2024)

e20005 Background: The 2023 report from the World Health Organization(WHO) ranked lung cancer (LC) as the top cause of cancer-related fatalities worldwide. Recently, minimally invasive procedures such as robotic-assisted thoracoscopic surgery (RATS) have been introduced as part of the treatment of some LC cases. Our study aims to bridge the understanding of potential sex-based disparities among LC patients undergoing lobectomy via RATS. Methods: We analyzed the 2016-2020 National Inpatient Sample (NIS) for adult lung cancer(malignant or carcinoma in situ) patients with a principal procedure code of lobectomy with RATS. Cases with underlying mycoses, mycobacterial infection, and pulmonary abscesses were excluded based on recommendations from prior studies. Multivariate regression models helped evaluate sex-based differences in several complications. Results: An estimated 26385 lung cancer patients underwent lobectomy via RATS, consisting of 56.68% females (14955 cases) and 43.32% males (11430 cases). Age differences were noted as females were younger (mean age 67.80 years vs. 69.14 years, p &lt; 0.01). We also found that females were less likely to report several complications, such as acute kidney injury (AKI) (3% vs. 6.6%, aOR 0.538, p &lt; 0.001), pneumonia (2.8% vs. 4.3%, aOR 0.725, p &lt; 0.001), post-procedural air leak (9.2% vs. 11.2%, aOR 0.797, p &lt; 0.001), post-procedural cardiac arrest (0.6 % vs. 1.6%, aOR 0.349, p &lt; 0.001), pulmonary embolism (0.2% vs. 0.5%, aOR 0.345, p &lt; 0.001), deep vein thrombosis (DVT)(1.5% vs. 2.2%, aOR 0.742, p: 0.003), atrial fibrillation (AF)(13% vs 21.7%, aOR 0.564, p &lt; 0.001), acute myocardial infarction (AMI) (0.2% vs. 0.5%, aOR 0.58, p:0.027), and death (0.3% vs. 0.9%, aOR 0.505, p &lt; 0.001). Notably, females were more likely to have an open procedure conversion (0.2% vs 0.1%, aOR 2.235, p:0.017). However, there is no significant difference between the two sexes regarding post-procedural pneumothorax and respiratory failure, atelectasis, supraventricular tachycardia, and events of acute ischemic stroke. Conclusions: Our most recent analysis confirms that among LC patients undergoing lobectomy via RATS, males were more prone to several complications than females. However, we also found that females were more likely to necessitate an open procedure conversion. We, therefore, advocate for further research to enhance our understanding of such disparities and strategies to address them effectively.
Assessment of carcinoembryonic antigen-related cell adhesion molecule 5 expression by immunohistochemistry in real-world clinical samples of non-small cell lung cancer.
Authors: Ying-Han Roger Hsu, Amna Almutrafi, Katrina Hueniken, Ming Sound Tsao
Journal: Journal of Clinical Oncology (2024)

e20013 Background: Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is an emerging target of antibody-drug conjugate therapy for non-small cell lung cancer (NSCLC). High expression of CEACAM5 has been reported in approximately 25% of patients with lung adenocarcinoma (Lefebvre AM, et al. Lung Cancer. 2023; 184:107356). However, CEACAM5 expression has not been systematically examined in a real-world patient population with NSCLC. In this study, we evaluated our experience in the assessment of CEACAM5 expression by immunohistochemistry (IHC) in routinely diagnosed clinical samples. Methods: We assessed the expression of CEACAM5 by IHC on clinical biopsy/resection samples of consecutively diagnosed NSCLC from September 2022 to June 2023 at our institution, using the anti-CEACAM5 clone 769 antibody assay protocol developed for tusamitamab ravtansine clinical trials. Only cases adequate for PD-L1 22C3 and Oncomine Comprehensive Assay v3 NGS assay were included. CEACAM5 expression was scored independently by three pathologists based on the method proposed by Lefebvre et al. Expression levels were categorized as high (≥ 50% tumor cells at ≥ 2+ intensity), moderate (1–49% tumor cells at ≥ 2+ intensity), and negative (0 or 1+ intensity). Interrater reliability was assessed by Kendall’s coefficient of concordance (KCC) and Fleiss’ Kappa. Discordant classification was reviewed with the final classification achieved by consensus. Association with PD-L1 TPS and NGS results was determined by Chi-squared test. Results: This study cohort consisted of 150 consecutively diagnosed NSCLC, including 133 adenocarcinomas and 17 squamous cell carcinomas. The samples were derived from both primary (n = 138) and metastatic sites (n = 12). Both membranous and cytoplasmic CEACAM5 expression was observed in neoplastic cells, but was consistently absent in nonneoplastic cells. The prevalence of consensus high CEACAM5 membranous expression was 21% (n = 32) overall, 20% in primary (n = 28) and 33% (n = 4) in metastatic sites. The level of interrater agreement across all categories was moderate (KCC = 0.77). Interrater agreement between high CEACAM5 expression versus moderate/negative categories combined was also moderate (Kappa = 0.60). Challenging features included the determination of staining intensity and mixed membranous and cytoplasmic staining pattern, and cases near the cut-offs of the defined categories. CEACAM5 expression was not associated with PD-L1 TPS (p = 0.42) or EGFR mutations (p = 0.44). Conclusions: Our data showed that approximately 20% of routinely diagnosed clinical NSCLC samples had high CEACAM5 expression by IHC. The interrater reliability on the determination of high CEACAM5 expression was moderate among the three pathologists. We highlighted the challenging aspects in the evaluation of this biomarker.
A randomized phase II trial of adjuvant pembrolizumab versus observation following curative resection for stage I non-small cell lung cancer (NSCLC) with primary tumors between 1-4 cm: Big Ten Cancer Research Consortium BTCRC-LUN18-153.
Authors: Greg Andrew Durm, Muhammad Furqan, Richard Delmar Hall, Alberto Chiappori, Patrick C. Ma, Lawrence Eric Feldman, Amit Kulkarni, Missak Haigentz, Apar Kishor Ganti, Dwight Hall Owen, Rachel E. Sanborn, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2024)

TPS8118 Background: Each year, approximately 35,000 patients are diagnosed with stage I lung cancer in the United States. Despite early detection, the 5-year overall survival for this population remains disappointing, ranging between 73-86% with recurrence rates from 18-38%. The current standard of care for stage I NSCLC is surgery alone followed by observation as prior trials of adjuvant chemotherapy in this subgroup have failed to show benefit. More modern therapies such as programmed death-1 (PD-1) inhibitors have not been evaluated in the stage I setting but have demonstrated significant improvements in pathologic complete response, event free survival, and overall survival when added to chemotherapy for patients with fully resected stage II and III disease. The use of PD-(L)1 inhibition has also demonstrated clinically and statistically significant improvements in OS in both unresectable stage III NSCLC following chemoradiation and in the metastatic setting. Given the activity of PD-(L)1 inhibition in nearly every other subset of NSCLC patients, we aimed to evaluate this therapy following resection in stage I NSCLC patients. Methods: This study is a randomized phase II multicenter trial of adjuvant Pembrolizumab versus observation alone following complete resection of stage I NSCLC with tumors between 1-4cm. The trial randomizes patients 1:1 to either Pembrolizumab 400mg IV every 6 weeks for up to 9 cycles or observation alone. Patients are stratified by PD-L1 score (PD-L1 ≥50% vs. &lt; 50%) and tumor size (1-2cm vs. &gt; 2-4cm), and they undergo repeat CT imaging every 12 weeks. The study is being conducted through the Big Ten Cancer Research Consortium, and there are currently 11 sites open to accrual with one additional site pending activation. The primary endpoint is disease free survival with secondary endpoints including OS, DFS at multiple timepoints (1-, 2-, and 3-years), and safety. The trial initially opened to accrual at the lead site, Indiana University, in May 2020, and enrollment is currently at 95 patients with a planned enrollment of 244. (NCT04317534) Clinical trial information: NCT04317534 .
A prospective phase II randomized clinical study of folic acid in the intervention of radiation esophagitis induced by concurrent chemoradiotherapy in lung cancer.
Authors: Hao Zhang, Yiying Zhu, Weiwei Ouyang, Shengfa Su, Zhu Ma, Qingsong Li, Wengang Yang, Xiaxia Chen, Bing Lu
Journal: Journal of Clinical Oncology (2024)

e20004 Background: To investigate the efficacy and safety of folic acid intervention in lung cancer patients with radiation esophagitis caused by concurrent chemoradiotherapy. Methods: It was a randomized, controlled, single-center clinical trial of 82 patients with stage N2~N3 lung cancer including SCLC and NSCLC were prospectively included. All patients were randomly divided into experimental and control group according to 1:1, and patients were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes (More than 2 cycles of chemotherapy were completed during the same period of radiotherapy or take targeted drugs at the same time, the cumulative radiation dose of chest lesions should exceed 40Gy). The experimental group took folic acid tablets 30mg/day orally at the beginning of radiotherapy until the end of radiotherapy, while the control group did not receive any drug intervention.When two groups appeared radiation esophagitis, the grading criteria for RTOG should be evaluated first, then according to the guidelines of symptomatic treatment.Esophageal toxicity was evaluated during radiotherapy, and improved RTOG and NCI-CTC ratings were performed weekly at the onset of radiation esophagitis and thereafter until 1 week after the end of radiotherapy. Results: The incidence of radiation esophagitis in the experimental group was low during the observation period, and the occurrence time of radiation esophagitis could be delayed in the experimental group, but there was no statistical significance between the two groups ( P=0.456). After folic acid intervention, the symptoms of pain and dysphagia of radiation esophagitis in the experimental group were significantly decreased, especially the RTOG grade and NCI-CTC improvement grade decreased significantly 2 weeks after the occurrence of radiation esophagitis( P=0.007, P=0.009). In the experimental group, it was found that the greater the change of hemoglobin before and after radiotherapy, the occurrence time of radiation esophagitis was about delayed, which was statistically significant(r=0.348, P=0.040).The correlation analysis of the control group showed that the change of body mass index was positively correlated with the onset time of radiation esophagitis(r=0.372, P=0.020);The lower the hemoglobin content after radiotherapy and the larger the hemoglobin difference before and after radiotherapy, the higher the highest incidence of radiation esophagitis(r= -0.454, P=0.004;r= -0.343, P=0.032). Conclusions: Oral folic acid can delay the onset of radiation esophagitis due to concurrent chemoradiotherapy and promote the recovery of radiation esophagitis to a certain extent,but can not interfere with the occurrence of radiation esophagitis.This trial is registered in Clinical Trials(NCT0529636). Clinical trial information: NCT0529636 .
Olaparib, AZD1390, ceralasertib, saruparib and consolidation durvalumab (CONCORDE) phase Ib platform study of novel DNA damage response inhibitor (DDRi) agents in combination with radiotherapy in non-small cell lung cancer (NSCLC).
Authors: Alastair Greystoke, Jamie B. Oughton, Sarah R Brown, Karl Butterworth, Victoria Coyle, Kevin Franks, Adam Hassani, Stephen Harrow, Matthew Hatton, Crispin T. Hiley, Jessica Kendall, Rachel Phillip, Matthew Norris, Oluwaseun Ojo, Paul Shaw, Fiona Walker, Huiqi Yang, Anthony J. Chalmers, Corinne Faivre-Finn
Journal: Journal of Clinical Oncology (2024)

TPS8119 Background: Lung cancer is the leading cause of cancer mortality globally, with cases projected to exceed 62,000 by 2035. Outcomes remain poor despite advances in radiotherapy (RT) technologies. Combining novel mechanism-based agents with RT could improve the therapeutic index. DNA inhibition of cellular response to radiation-induced DNA damage can overcome intrinsic radio resistance and poses a promising strategy. Methods: CONCORDE is an open label, randomised, multi-arm, phase Ib, clinical trial opened to accrual in 11 UK hospitals designed to assess multiple DDRi in combination with radical thoracic RT (60Gy in 30 fractions over 6 weeks). Patients are randomised 3:1 to RT+/-DDRi. The study utilises an adaptive Bayesian model-based approach to dose escalation aiming to identify the recommended phase II dose for each treatment combination. Two arms will deliver up to 12 months consolidation durvalumab+/-DDRi following RT. Patients are eligible based on key criteria: not suitable for concurrent chemotherapy RT, inoperable, stage IIB/III NSCLC, performance status (KPS≥70). The dose limiting toxicity (DLT) period for treatment-related toxicities is 13.5 months post start of RT treatment, with most toxicities expected within the first 4.5 months (short DLT period). At least one patient must complete the short DLT period before dose escalation. A RT-alone calibration arm aids toxicity attribution. This trial is in progress: CONCORDE-A (olaparib (PARP inhibitor)), CONCORDE-B (AZD1390 (ATM inhibitor)), CONCORDE-C (ceralasertib (ATR inhibitor) followed by consolidation durvalumab+/-ceralasertib) and CONCORDE-E (AZD5305/saruparib (PARP1select inhibitor) followed by consolidation durvalumab) are open to accrual as of 24/11/2023. 57 of 74 registered participants have been randomised across 4 study arms. Of those 57 randomised: 55 started treatment: 20 received RT-alone, 12 received olaparib+RT, 14 received AZD1390+RT, 6 received ceralasertib+RT, 3 received AZD5305+RT and 2 withdrew. CONCORDE continues to recruit to the target sample size of 160 (40/arm) and welcomes further UK centres. A parallel multimodality translational program to identify biomarkers of treatment response, toxicity and the impact on the immune system are in development. Biomarkers of interest include plasma toxicity markers, immune cell profiling, radiomics and ctDNA. Clinical trial information: 10142971.
Efficacy and safety of aumolertinib combined with or without chemotherapy as an adjuvant treatment for stage II-IIIA non-small cell lung cancer following complete tumour resection: The first third-generation EGFR-TKI versus chemotherapy phase III clinical study (APEX).
Authors: Feng Tan, Zhijie Wang, Gang Feng, Daqiang Sun, Haitao Ma, Tao Jiang, Sihua Wang, Hongxu Liu, Weidong Hu, Wei Liu, Yuming Zhu, Hecheng Li, Hao Peng, Qingchen Wu, Weiyu Shen, Shun Xu, Quanren Zhang, Yongtao Han, Jie Wang, Shugeng Gao
Journal: Journal of Clinical Oncology (2024)

TPS8117 Background: Patients with stage II-III A non-small cell lung cancer (NSCLC) can benefit from adjuvant targeted therapy. ADAURA study shows a remarkable advantage of disease-free survival (DFS). However, there are still unresolved clinical issues. Firstly, the control group in the trial is received placebo, making it impossible to directly compare the efficacy of adjuvant targeted therapy with the traditionally recommended adjuvant chemotherapy in guidelines. Thus, it cannot address the direct comparison of third-generation TKIs with the current standard therapy (chemotherapy). Secondly, the necessity of combining chemotherapy with adjuvant targeted therapy need to explored. Aumolertinib is a third-generation epidermal growth factor receptor- tyrosine kinase inhibitor (EGFR-TKI) that potently and selectively inhibits EGFR sensitizing and EGFR T790M resistance mutations. This study aims to evaluate the efficacy and safety of aumolertinib combined with or without chemotherapy as adjuvant treatment for EGFR-sensitive mutations stage II-III A non-squamous NSCLC patients. Methods: This is a multicenter, randomized, open label, phase III study. Patients with histologically confirmed stage II-III A non-squamous NSCLC harboring EGFR mutations without prior EGFR TKI treatment and R0 resection are eligible for this study. The performance status (Eastern Cooperative Oncology Group) is 0 or 1. This trial prepared to enroll approximately 606 patients, will be randomized (3:2:1) to receive either aumolertinib alone (110mg, po, once daily) or aumolertinib (110mg, po, once daily) plus pemetrexed (500mg/m2, iv) and cisplatin (500mg/m2, iv) or pemetrexed (500mg/m2, iv) plus cisplatin (500mg/m2, iv). The first patient was enrolled on August 2, 2021. The primary end point is DFS, The secondary endpoints include 2, 3, 4, 5-year DFS rates, 5-year overall survival (OS), OS, safety and quality of life. Adverse effects were graded per CTCAE v.4.0. This trial is registered as NCT04762459. Clinical trial information: NCT04762459 .