tbuckley/cabot-search huggingface dataset:
Histopathological features of SMARCA4-deficient thoracic malignancies: Data from resource-limited setting.
Authors: Nune Karapetyan, Davit Zohrabyan, Parandzem Khachatryan, Liana Safaryan, Lilit Harutyunyan, Armen Avagyan, Aramayis Galumyan, Gevorg Voskanyan, Gor Geghamyan, Sergo Mkhitaryan, Mikayel Arustamyan, Meri Ghayamyan, Sona Karamyan, Mariam Khachatryan, Armen Arzumanyan, Mariam Hovhannisyan, Samvel Bardakhchyan, Armen Mkhitaryan
Journal: Journal of Clinical Oncology (2024)

e20045 Background: SMARCA4 deficient tumors are rare malignancies that develop due to inactivating mutation in switch/sucrose-nonfermenting chromatin remodeling complexes (SWI/SNF). This is an aggressive type of non-small cell lung cancer (NSCLC) with a poor prognosis and mediocre treatment response. The trials and observational research on SMARCA4 deficient thoracic malignancies are lacking, especially in limited resource settings. This study aims to analyze pathological and immunohistochemical (IHC) profiles of patients with SMARCA4 deficient thoracic malignancies in Armenia. Methods: The current research utilizes a retrospective cohort single-center study design. The study setting was the only pathology center in Armenia that runs an IHC panel for SMARCA4/BRG1 protein evaluation. For data collection purposes, a census sampling has been done and all the pathology reports of SMARCA4 deficient thoracic malignancies were reviewed. The study timeframe was from 24 February 2021 up to 11 December 2023. Descriptive statistics through portions were done to analyze the data. Results: In total, 19 patients with SMARCA4 deficient thoracic malignancies were diagnosed. The male-to-female ratio was 15:1 and the median age was 63 years (range: 50-73 years). Of those cases, 21% (n = 4) were excluded from the current analysis as histopathological examination of those tissue samples was not performed. The diagnosis was based on an IHC evaluation to obtain a second opinion. The tissue histopathological architecture was represented: 60% (n = 9) solid, 6.67% (n = 1) trabecular, and 6.67% (n = 1) papillary. Of those samples, 66.7% (n = 10) had hyperchromatic/polymorphic nuclei and 33.3% (n = 5) pleomorphic nuclei. Similarly, the evaluated sample cells have 53.3% (n = 8) eosinophilic, 13.3% (n = 2) clear, and 13.3% (n = 2) scant cytoplasm. All 19 cases were included in the descriptive analysis of the IHC profile as examinations were performed for all the subjects. The IHC profile of the cohort is presented in the table. Ki67 was checked in 47.4% (n = 9) of cases with 70-75% median expression. In general, the most frequently examined markers were TTF1, p40, Chromogranin, and AE1/3. Conclusions: In conclusion, the study shed light on SMARCA4 thoracic tumors spread in Armenia. Considering the rarity of the disease, further research is required to investigate the actual prevalence of SMARCA4 deficient thoracic tumors and treatment approaches in Armenia. [Table: see text]
Neoadjuvant immuno-chemotherapy in resectable non-small cell lung cancer: A retrospective cohort study.
Authors: Saurav Verma, Mark David Vincent, Morgan Black, Rahul Nayak, Matthew Cecchini, Richard Malthaner, Jacques Raphael, Richard Inculet, Dalilah Fortin, Philip Blanchette, Sara Kuruvilla, Mehdi Qiabi, Jawaid Younus, Daniel Adam Breadner
Journal: Journal of Clinical Oncology (2024)

e20077 Background: Neoadjuvant (NA) nivolumab-chemotherapy (nivo-chemo) has shown an improved survival and pathological complete response (pCR) rate, vs chemo alone, in early-stage, resectable non-small cell lung cancer (NSCLC). Nevertheless, there is a paucity of real-world data. Methods: We performed a real-world, retrospective analysis of outcomes and toxicities in patients with resectable NSCLC (stage IB-IIIA; EGFR/ALK alterations excluded) treated with three cycles of NA nivo-chemo followed by surgery at a single, tertiary-level Canadian cancer centre from September 2022 to September 2023. Results: Fifteen patients were treated with NA nivo-chemo. The median age was 70 years (range, 58 to 78) and 66% were males. 20% (n-3) and 40% (n-6) had N1 and N2 nodes, respectively. All patients completed three cycles of NA nivo-chemo. Objective response rate was 73% (n-11); including 1 complete response. Progression was noted in two patients (the CT predated initiation of treatment by more than 8 weeks in these patients). The median time to surgery was 10.6 weeks (range, 6-17.5). 80% patients (n-12) had a surgery (1 pneumonectomy, 11 lobectomies); and of these, 83% (n-10) are on surveillance while two patients had an event (death or progression). All (n-11) had R0 resection except one. 33% patients (n-5) had a pCR, including two with stage IIIA disease (PDL1 TPS &lt; 1% in three patients, PDL1 TPS ≥ 50% in two patients). 60% patients were started at a reduced chemo dose in cycle 1. 25% patients required further dose reduction. Grade 3 or 4 toxicities were seen in 25% patients (n-4) (neutropenia (n-2), febrile neutropenia (n-1) and pneumonitis (n-1)). Surgical complications were seen in 33% patients (n-5), including death in one patient due to postoperative intrathoracic bleed. Conclusions: NA nivo-chemo in resectable NSCLC is safe and associated with improved pCR rate. A few patients may progress on NA treatment or have a grade 3-5 toxicity precluding curative surgery. Hence, individualized informed decisions should be made. There is an unmet need of biomarkers/models that can predict pCR/toxicity for better patient selection. [Table: see text]
Fetal adenocarcinoma: An NCDB analysis of socioeconomic and demographic factors.
Authors: Emily Han, Mark Moroz, Suraj Puvvadi, Angel Joseph, Peter T. Silberstein, Craig Heise, Beau Hsia
Journal: Journal of Clinical Oncology (2024)

e20076 Background: Fetal adenocarcinoma (FA) is a rare subtype of lung neoplasia whose structure is similar to a developing fetal lung. Chest x-ray is valuable for diagnosis as 25 - 40% of patients with FA are asymptomatic. FA is classified into low-grade and high-grade, predominantly occurring in children and older males with a smoking history. The rarity of FA suggests that evaluating its diagnostic patterns could expand awareness of its epidemiology. Impactful demographic factors of FA were established through analysis of the National Cancer Database (NCDB). Methods: The 2004 - 2020 National Cancer Database (NCDB) was utilized to perform a retrospective analysis of all 120 patients with a histologically confirmed diagnosis of FA (ICD-O-3 Code 8333). Descriptive statistics were employed to examine demographic factors, including sex, age, race, Hispanic ethnicity, urban/rural residence, Charlson-Deyo comorbidity score (CDCS), and treatment facility type. Additionally, regression analysis was utilized to demonstrate incidence trends. Exclusion criteria included missing values. Results: The NCDB identified 120 patients from 2004 - 2020. Over this time period, there was a slightly increasing incidence of patients diagnosed per year (R2 = 0.4461). Represented age at diagnosis featured negative skewness (-0.8), and the mean age was 54.4 years (95% CI = 51.2 - 57.6, SD = 17.6). Most patients were female (57%), White (76%), and non-Hispanic (95%). The vast majority of patients (85%) resided in metropolitan areas, with a slight majority of patients (53%) hailing from areas of 1 million population or more. Regions of the United States were well-represented, with a plurality of patients from the South Atlantic (21%). Most patients were diagnosed at Stage I (56%) and had a CDCS of 0 (61%). The primary tumor site was the upper lung lobes, and most (83%) patients underwent surgery as primary treatment. Multiple facility types were utilized in the care of patients, including research programs (42%), comprehensive community cancer center programs (30%), and integrated network cancer programs (25%). The 30-day mortality rate was 1%, comparable to the 90-day mortality rate of 3%. Five years after diagnosis, 60% of patients were alive. Conclusions: To the best of our knowledge, this is the first NCDB analysis to examine the sociodemographic factors concerning prognosis in patients with FA. Our results are consistent with previous studies finding that patients with low-stage FA tend to have favorable outcomes. Our study is the first documentation of location demographics of patients with FA: Most patients live in metropolitan counties along the Atlantic Coast. Future investigations on the prognostic significance of demographic and socioeconomic factors should be performed to optimize treatment approaches for improved mortality rates of diverse patients with FA.
A novel strategy for detecting mutations from circulating tumor DNA with blood tissue only.
Authors: Jiale Wen, Zhi Zheng
Journal: Journal of Clinical Oncology (2024)

e20031 Background: Molecular Residual Disease (MRD) test detects tumor-specific mutations in circulating tumor DNA (ctDNA), which can indicate the risk of tumor recurrence. However, without tumor-specific mutations, detecting mutations in blood tissue alone is extremely challenging due to the low concentration of ctDNA in blood. To address this challenge, we proposed an innovative mutation filtering and calling strategy by simulating noise’s distribution and quality assessment to greatly boost the performance. Methods: We performed 406 pairs of MRD tests on both tumor and blood tissue of postoperative patients with mixed cancer types, including lung, gastrointestinal (GI), hepatobiliary, and pancreatic. Patients that possess one or more tumor-specific mutations in their blood tissue were classified as recurrence high-risk (n = 66), others were classified as recurrence low-risk (n = 340). All sequence data were analyzed using both traditional and proposed method. In the traditional method, VAF threshold, end-reads, multiple-align reads and population frequencies were used as filtering criteria. While in the proposed method, VAF threshold was excluded and two new parameters were introduced: The distribution of variant allele frequency (VAF) of sequencing noise, which simulated 42 healthy individuals’ background noise with conf &gt; 0.995; The normalized proportion of supported unique and total variants, to assess the likelihood of mutations originated from ctDNA. Results: Among 406 patients of mixed tumor types, the traditional approach barely reached a sensitivity of 39.4% and a specificity of 89.1%, while our strategy achieved a sensitivity of 71.2% and a specificity of 80.9%. Particularly among the 92 patients with gastrointestinal tumor, by filtering specific noise caused by the MRD panel (e.g. multi-alignment error of MUC gene family), we further boost the sensitivity from 47.1% to 82.4% with a loss of specificity from 93.3% to 90.7%. Moreover, among 248 patients with lung tumors, the sensitivity and specificity between traditional approach and proposed method were 15.8%, 93.9%, and 52.6%, 90.0% respectively, which might be caused by the low recurrence rate in the patient cohort (19 out of 248). Conclusions: The novel strategy based on simulated noise distribution and read quality assessment surpasses the traditional threshold-based approaches in mutation detection, especially in deep sequencing like MRD tests. The findings of the study indicate that the recurrence monitoring strategy is applicable across various tumor types and exhibits superior performance in GI tumor, albeit with certain limitations. In conclusion, this study boosts the feasibility of MRD as a non-invasive alternative for tissue biopsy by providing a novel mutation filtering strategy, which further strengthen the potential of MRD testing in enhancing cancer patients’ long-term prognosis and treatment.
Lung and bronchus cancer in young females: Exploring sex disparities across diverse racial and ethnic groups in the U.S. (2000-2020).
Authors: Sharon Hechter, Anish Kumar Kanukuntla, Christina Eliachevsky, Sophia Ji, Jennifer Appiah, Ibrahim Alnaser, Ambica Nair, David B. Greenberg
Journal: Journal of Clinical Oncology (2024)

e20048 Background: Lung and bronchus cancer incidence rates have been reported to be higher among females than males under the age of 50, particularly after 2004. The first e-cigarette device emerged in 2003, raising questions about its potential impact on cancer incidence in females compared to males and its connection to the sudden rise in female cases. This study aims to investigate sex differences in cancer incidence across diverse racial and ethnic groups, aiming to determine whether these variations stem from biological factors or unexplored environmental exposures. Methods: Cancer incidence data from the Surveillance, Epidemiology, and End Result (SEER) program (2000-2020) were utilized to analyze female-to-male incidence rate ratios (FM IRR) for young-onset lung and bronchus cancer diagnosed before the age of 50. The data was stratified by race and ethnicity (non-Hispanic White, non-Hispanic Black, non-Hispanic Asian/Pacific Islander, American Indian/Alaskan Native, and Hispanic) and age-standardized to the 2000 U.S. population. Results: In the period from 2000 to 2020, 41,066 patients with lung and bronchus cancer under the age of 50 were identified. Incidence trends showed a consistent decrease each year, reaching the lowest rates in 2020 (2.1 per 100,000 cases) and the highest in 2000 (4.9 per 100,000 cases). Males accounted for 49.4% (20,303), while females constituted 50.6% (20,763). Despite the overall declining trend, FM IRR steadily increased post-2004, exhibiting a constant rise between 2005 and 2020. Non-Hispanic White comprised 65.9% of the cases, with the second and third largest groups being Non-Hispanic Black (15.3%) and Hispanic (9.62%). Incidence rates were highest among non-Hispanic Black (4.9 per 100,000 cases), followed by non-Hispanic White (4.2 per 100,000 cases), and lowest in the Hispanic population (1.6 per 100,000 cases). Young-onset lung and bronchus cancer diagnosed before age 50 showed a female predominance after 2004, with the Hispanic population having the highest FM IRR between 2000 and 2020 (1.13), followed by Non-Hispanic American Indian/Alaska Native (1.09) and Non-Hispanic White (1.02). There was a lower FM IRR among Non-Hispanic Black and Non-Hispanic Asian/Pacific Islander (0.83) and (0.96), respectively. Conclusions: The FM IRR for young-onset lung and bronchus cancer exhibited variations among racial and ethnic groups, with the highest rates observed among the Hispanic population. This study was limited by the absence of data on smoking habits and other environmental factors. Further research is needed to investigate the influence of e-cigarettes and other environmental factors on the incidence of lung and bronchus cancer, considering variations by sex.
Brain metastases in patients with pleural mesothelioma receiving dual checkpoint blockade compared to single-agent checkpoint blockade or chemotherapy.
Authors: Margaret Stalker, Suzanne Walker, Emily S. Lebow, Evan P. Anderson, Leonid Roshkovan, Sharyn I. Katz, Leslie Litzky, Andrew R. Haas, Sunil Singhal, Corey J. Langer, Keith A. Cengel, Melina Elpi Marmarelis
Journal: Journal of Clinical Oncology (2024)

e20093 Background: Immunotherapy (IO) has emerged as a treatment option in pleural mesothelioma (PM). Historically, brain metastases (BM) in PM were rare, thus brain imaging is not routine practice or included in guidelines. We characterize the incidence of BMs by type of treatment received. Methods: In this retrospective analysis,adult patients with PM treated at the Hospital of the University of Pennsylvania between 1/1/2015- 8/31/2023 were included. Patient demographic data, treatment, brain imaging and clinical history were extracted from the electronic medical record.A two-tailed Z score with alpha 0.05 was used to determine a difference in proportion of patients with BM by treatment group. Results: 290 patients were included in the study. 154 (53.1%) were treated with chemotherapy (CT), 94 (32.4%) were treated with pembrolizumab (pembro), 39 (13.4%) were treated with ipilimumab + nivolumab (ipi/nivo), and 3 (1.0%) were treated with another IO. A higher proportion of patients treated with ipi/nivo developed BM compared to those treated with pembro alone (4/39, 10.3% vs 2/94, 2.1%; Z score p= 0.038). None of the 154 patients treated with CT developed BM. All BMs were detected due to symptoms. Of the six patients that developed BM, the median age was 72.5 (range 47-80), 83% were male, 67% identified as Caucasian, and there was an even distribution of histology with 33% each of epithelioid, biphasic, and sarcomatoid. All patients received IO most recently or were currently on it when BM developed. Median time to BM from start of immunotherapy was 144.5 days (range 2-913 days). On imaging, all 6 patients had edema surrounding the brain metastases and 4 also showed hemorrhage. Survival after development of BM was poor (Table1). Four patients (67%) underwent surgery for the BM, while all patients received brain radiation. Two patients received whole brain radiation therapy (WBRT), while four patients received stereotactic radiosurgery (SRS) to a median of four brain metastases (range 1-7). Three patients developed subsequent intracranial progression (out-of-field) including one with rapid intracranial progression 20 days post-radiation. Conclusions: In this large retrospective study of patients with PM treated with systemic therapy, BM was most prevalent in those patients receiving ipi/nivo compared to pembro alone and not seen in those receiving chemotherapy. The presence of edema suggests a possible immune infiltrate while on IO (correlative studies in progress). Brain imaging should be considered prior to starting IO in patients with PM. [Table: see text]
A post-hoc analysis of outcomes of patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) who received oral azacitidine (Oral-AZA) maintenance therapy in the QUAZAR AML-001 study.
Authors: Maria Teresa Voso, Stéphane De Botton, Michael Pfeilstöcker, Angela Figuera Alvarez, Kefeng Wang, Wendy L. See, Manuel Ugidos Guerrero, Daniel Lopes de Menezes, Erica Petrlik, Thomas Prebet, Gail J. Roboz
Journal: Journal of Clinical Oncology (2024)

6522 Background: AML-MRC represents 25%–34% of all AML cases, and patients with this AML subtype generally have poor outcomes. In this subanalysis of the QUAZAR AML-001study, we report outcomes of patients with AML-MRC who received Oral-AZA vs placebo (PBO). Methods: QUAZAR AML-001 was a phase 3 study of Oral-AZA maintenance therapy in patients with AML in first remission after intensive chemotherapy who were not eligible for hematopoietic stem cell transplantation (HSCT). Patients ≥ 55 years of age with AML and intermediate- or poor-risk cytogenetics received Oral-AZA 300 mg or PBO QD for 14 d per 28-d cycles. In this analysis, WHO 2008 criteria were used to identify patients with secondary AML and/or patients with AML-MRC (both groups are referred to as AML-MRC in this analysis). Data on mutational profiles at diagnosis were not available. Overall survival (OS) from time of randomization to time of death from any cause after censoring for HSCT, and relapse-free survival (RFS) from time of randomization, were calculated using the Kaplan–Meier method. Duration of measurable residual disease (MRD) negativity achieved on treatment was calculated from the first MRD-negative assessment. Results: Overall, 101/472 patients had AML-MRC; 56/238 (23.5%) patients in the Oral-AZA arm and 45/234 (19.2%) patients in the PBO arm. Karyotype/cytogenetics data at diagnosis were available for 87/101 (86.1%) patients with AML-MRC and 331/371 (89.2%) patients with non-AML-MRC. A greater proportion of AML-MRC than non-AML-MRC patients had poor-risk cytogenetics (20/101 [19.8%] vs 46/371 [12.4%]), del(5q) (10/87 [11.5%] vs 9/331 [2.7%]), and monosomy 7/del(7q) (9/87 [10.3%] vs 14/331 [4.2%]). Median OS did not significantly differ in patients with AML-MRC vs non-AML-MRC in either treatment arm (Oral-AZA: 19.9 mo vs 25.1 mo, P = 0.2694; PBO: 14.8 mo vs 14.9 mo, P = 0.2099). In both treatment arms, the median RFS was inferior for patients with AML-MRC vs non-AML-MRC (Oral-AZA 7.5 mo vs 10.5 mo, P = 0.0430; PBO: 3.7 mo vs 4.9 mo, P = 0.0109). Oral-AZA significantly prolonged median OS and RFS, and the duration of MRD negativity for patients with AML-MRC compared with PBO (Table). Conclusions: Oral-AZA significantly improved OS and RFS compared with PBO for patients with AML-MRC indicating that Oral-AZA maintenance is an effective treatment option for these patients with particularly poor prognosis. Clinical trial information: NCT01757535 . [Table: see text]
ViTR-SP: A CT-based vision transformer model for prediction of pneumonitis in patients with non-small cell lung cancer who received thoracic radiotherapy and immunotherapy.
Authors: Linlin Yang, Butuo Li, Taotao Dong, Linlin Wang
Journal: Journal of Clinical Oncology (2024)

e20034 Background: The combination of thoracic radiotherapy (TRT) and immunotherapy accompanied by the accumulation of pulmonary toxicity. This study aimed to construct a deep radiomics model based on sequential computed tomography (CT) images for radioimmune-associated pneumonitis prediction in non-small cell lung cancer (NSCLC) patients treated with TRT and immune checkpoint inhibitors (ICIs). Methods: Three models were constructed based on a vision transformer (ViT) network using sequential chest CT images, tumor-mask and lung-mask as inputs, respectively. NSCLC patients treated with TRT and ICIs at Shandong Cancer Hospital and Qilu Hospital were included for model training and external validation, respectively. The image-level model was trained based on ViT to identify predictive images, and the image-level probability distribution were performed. Then, a ViT-Recursive Neural Network (ViT-RNN) model framework was constructed at the patient-level to integrate the image-level information to derive the final prediction, which was evaluated in an independent validation cohort. Results: A total of 230 NSCLC patients from Shandong Cancer Hospital were randomly assigned in a 7:3 ratio for model training and validation, respectively. Another 42 patients from Qilu Hospital were used as an independent external validation cohort. The ViT-RNN model for symptomatic pneumonitis (ViTR-SP) based on sequential CT images achieved better area under curve (AUC), sensitivity, and specificity of 0.725, 0.750, and 0.886 than lung-mask based model (0.575, 0.625, and 0.705) and tumor-mask based model (0.658, 0.667, and 0.773) in the internal validation set. In the external validation set, the proposed model achieved the AUC, sensitivity, and specificity of 0.654, 0.818, 0.727, while the lung-mask and tumor-mask based models had the AUC, sensitivity, and specificity of 0.540, 0.545, 0.677, and 0.630, 0.545, 0.742, respectively. The performance of the model was improved after integrating clinical features, with internal and external validation AUC of 0.782 and 0.672, respectively. Conclusions: In conclusion, the clinical combined ViTR-SP neural network risk prediction model based on sequential chest CT images can be used for predicting the risk of developing radioimmune-associated pneumonitis in NSCLC patients.