Non-small Cell Carcinoma Research Articles

The success rates of clinical cancer next-generation sequencing based on pathologic diagnosis: Experience from a single academic laboratory.

This article aims to establish the relationship between pathologic diagnosis and the rate of success in cancer next-generation sequencing testing. Clinical next-generation sequencing results performed for solid tumors were reviewed. The rate of success was analyzed in the context of tumor type and accompanying variables. Out of 683 total specimens, 533 (78.0%) underwent successful sequencing. The rate of success was 91.8% for ovarian carcinomas, 87.5% for lung non-small cell carcinomas, 82.0% for colorectal adenocarcinomas, 78.3% for melanomas, 75.9% for breast carcinomas, and 64.7% for pancreatic adenocarcinomas. For specimens that successfully underwent sequencing, pancreatic adenocarcinomas had the lowest median tumor proportion and somatic RAS and TP53 mutation allele fractions compared with other tumor types. Cytology specimens had a 33.3% success rate for pancreatic adenocarcinomas (5 of 15) and a 93.3% success rate for lung carcinomas (14 of 15). Compared with tissue from primary sites, tissue from metastatic sites showed a higher success rate for pancreatic adenocarcinomas and lower success rates for colorectal adenocarcinomas and melanomas. The success rate of cancer next-generation sequencing testing is dependent on pathologic diagnosis, tissue site, and diagnostic procedure. Understanding which specimens are at higher risk for failing molecular testing may help pathologists and clinical care teams optimize tissue acquisition and usage for patient care.

SDPS-42 METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) AND BRAIN EDEMA: A TOPOGRAPHICAL AND CLINICOPATHOLOGIC INVESTIGATION

Abstract Tumor-associated vasogenic brain edema is a well-known contributor of morbidity and mortality in patients with metastatic disease to the brain. It is widely accepted that metastatic disease to the brain is associated with extensive edema and can cause increased symptomatology such as pain, neurologic deficit, and elevated intracranial pressure depending on extent and location. We present a retrospective artificial intelligence (AI) mediated analysis of radiological and clinicopathologic data including specific molecular markers, presenting symptoms, and tumor location of 86 patients with non-small cell carcinoma of the lung (NSCLC) and brain metastases who underwent surgical resection and were not previously on steroids. We found that overall, tumors in all locations demonstrated a mean 10:1 edema to tumor ratio (ETR) and an occipital tumor location was associated with a significantly elevated ETR. Within our cohort there were no other factors that were significantly associated with ETR. This study demonstrates a proof of concept that NSCLC is associated with significant peritumoral edema and that topographical factors may be associated with increased extent of edema.

Evaluation of automated sample preparation system for lymph node sampling.

Endobronchial ultrasound-guided transbronchial fine needle aspiration (EBUS-FNA) has revolutionized the diagnostic and staging approach to non-small cell carcinoma and thoracic lymphadenopathy. However, obstacles to efficacy of rapid on-site evaluation (ROSE) of the samples include variability in sample quality and slow and cumbersome process in the procedure room leading to extended procedure time. The purpose of this pilot study was to evaluate the feasibility and specimen quality of lymph node biopsies prepared through a novel automated system for automated fixation, drying and staining compared to standard slide preparation method. We performed a prospective, single-center pilot feasibility study of patients undergoing EBUS. Samples were split into conventional standard of care (SOC) slide preparation and preparation using the device ("instrument"). Pathologists compared the SOC slides to the slides prepared by the automated system and assessed the following metrics: nuclear and cytoplasmic quality, presence of debris/artifact, staining quality, creation of a monolayer, and ease of adequacy/diagnosis assessment. A score between 1 (lowest quality) and 3 (highest quality) was assigned to the above metrics. Sixty patients were recruited. One to three lymph nodes were sampled for each patient for a total of 72 samples collected. The mean scores of each assessment category showed no statistical difference between the two preparation techniques except for improved monolayer creation in the instrument samples. Thirty of thirty-one (96.8%) paired samples in the final analysis showed diagnostic equivalency between the automated slides and conventional slides; the discordant pairing was reported to be suspicious on the instrument sample and atypical on the SOC. Study results suggest that slides prepared by the automated system are of adequate quality for adequacy assessment with diagnostic concordance when compared to SOC slides.

Palliative Care Case Report: A Man with End Stage Lung Cancer with Brain Metastases

INTRODUCTION : Lung cancer accounts for 13% of malignancies in the world and the most common type of cancer suffered by men in Indonesia. The 5-year survival rate for patients with lung cancer is only 18.1%. About 25-30% will develop brain metastases. Overall palliative care is needed including biologically targeted therapy, chemotherapy, stereotactic radiosurgery (SRS), surgery in selected cases, and whole brain radiotherapy treatment (WBRT). Rare studies that take into account surgical palliation in advanced NSCLC. It has been demonstrated that metastaticectomy generally improves survival and, in some patients, even long-term survival. CASE REPORT : A 65-year-old male patient with Non-Small Cell Carcinoma favor Lung Adenocarcinoma and cerebellum metastases. The patient underwent surgery to remove a brain tumor. The patient received 8 radiotherapies and Erlotinib chemotherapy for 4 cycles for 6 months. The dose of Erlotinib 150g/24 hours was used in the first month. The dose was reduced in the 2nd to 6th month to 100g/24 hours. Assessment of palliative care was carried out using the Karnopsky Questionnaire, Fatigue Severity Scale (FSS), and Palliative Performance Scale (PPS). CONCLUSION : . Despite major improvements in the way lung cancer patients are treated in recent years, morbidity and death rates are still high. Palliative care (PC) is an approach to treating patients with life-threatening diseases, one of which is lung cancer

Primary Pulmonary Carcinomas with Spindle and/or Giant Cell Features: A Review with Emphasis in Classification and Pitfalls in Diagnosis.

Primary carcinomas of the lung are vastly represented by the conventional types of adenocarcinomas or squamous cell carcinomas. However, there are other types of non-small cell carcinomas that although uncommon represent a meaningful group that often pose a problem not only in diagnosis but also in classification. Spindle cell and/or giant cell carcinomas, although uncommon represent an important group of primary lung carcinomas. Important to highlight is that current criteria are rather ambiguous and likely not up to date, which renders the classification of these tumors somewhat more obscure. In addition, with the daily use of immunohistochemical stains, the classification of these tumors may also pose a different problem in the proper allocation of these tumors. Proper classification is highly important in the selection process that takes place using such material for molecular analysis. The current molecular characteristics of these tumors are limited and lack more in-depth studies and analyses that can provide specific targets for the treatment of patients with these tumors. The current review attempts to highlight the shortcomings in the current classification and definitions of these neoplasms as well as the more current view regarding these tumors when the use of immunohistochemical stains is employed.

Histology-Validated Dielectric Characterisation of Lung Carcinoma Tissue for Microwave Thermal Ablation Applications.

Microwave thermal ablation is a promising emerging treatment for early-stage lung cancer. Applicator design optimisation and treatment planning rely on accurate knowledge of dielectric tissue properties. Limited dielectric data are available in the literature for human lung tissue and pulmonary tumours. In this work, neoplastic and non-neoplastic lung dielectric properties are characterised and correlated with gross and histological morphology. Fifty-six surgical specimens were obtained from twelve patients undergoing lung resection for lung cancer in University Hospital of Galway, Ireland. Dielectric spectroscopy in the microwave frequency range (500 MHz-8.5 GHz) was performed on the ex vivo lung specimens with the open-ended coaxial probe technique (in the Department of Pathology). Dielectric data were analysed and correlated with the tissue histology. The dielectric properties of twelve lung tumours (67% non-small cell carcinoma (NSCC)) and uninvolved lung parenchyma were obtained. The values obtained from the neoplastic lung specimens (relative permittivity: 52.0 ± 5.4, effective conductivity: 1.9 ± 0.2 S/m, at 2.45 GHz) were on average twice the value of the non-neoplastic lung specimens (relative permittivity: 28.3 ± 6.7, effective conductivity: 1.0 ± 0.3 S/m, at 2.45 GHz). Dense fibrosis was comparable with tumour tissue (relative permittivity 49.3 ± 4.6, effective conductivity: 1.8 ± 0.1 S/m, at 2.45 GHz).

Deciphering a cell death-associated signature for predicting prognosis and response to immunotherapy in lung squamous cell carcinoma

BackgroundLung squamous cell carcinoma (LUSC) is a subtype of non-small cell carcinoma, accounting for about 30% of all lung cancers. Yet, the evaluation of prognostic outcome and therapy response of patients with LUSC remains to be resolved. This study aimed to explore the prognostic value of cell death pathways and develop a cell death-associated signature for predicting prognosis and guiding treatment in LUSC.MethodsTranscriptome profiles and corresponding clinical information of LUSC patients were gathered from The Cancer Genome Atlas (TCGA-LUSC, n = 493) and Gene Expression Omnibus database (GSE74777, n = 107). The cell death-related genes including autophagy (n = 348), apoptosis (n = 163), and necrosis (n = 166) were retrieved from the Kyoto Encyclopedia of Genes and Genomes and Gene Ontology databases. In the training cohort (TCGA-LUSC), LASSO Cox regression was used to construct four prognostic signatures of respective autophagy, apoptosis, and necrosis pathway and genes of three pathways. After comparing the four signatures, the cell death index (CDI), the signature of combined genes, was further validated in the GSE74777 dataset. We also investigated the clinical significance of the CDI signature in predicting the immunotherapeutic response of LUSC patients.ResultsThe CDI signature was significantly associated with the overall survival of LUSC patients in the training cohort (HR, 2.13; 95% CI, 1.62‒2.82; P < 0.001) and in the validation cohort (HR, 1.94; 95% CI, 1.01‒3.72; P = 0.04). The differentially expressed genes between the high- and low-risk groups contained cell death-associated cytokines and were enriched in immune-associated pathways. We also found a higher infiltration of naive CD4+ T cells, monocytes, activated dendritic cells, neutrophils, and lower infiltration of plasma cells and resting memory CD4+ T cells in the high-risk group. Tumor stemness indices, mRNAsi and mDNAsi, were both negatively correlated with the risk score of the CDI. Moreover, LUSC patients in the low-risk group are more likely to respond to immunotherapy than those in the high-risk group (P = 0.002).ConclusionsThis study revealed a reliable cell death-associated signature (CDI) that closely correlated with prognosis and the tumor microenvironment in LUSC, which may assist in predicting the prognosis and response to immunotherapy for patients with LUSC.

Study on the material basis and action mechanisms of sophora davidii (Franch.) skeels flower extract in the treatment of non-small cell lung cancer

Ethnopharmacological relevanceSophora davidii (Franch.) Skeels Flower (SDF) is a characteristic folk medicine in Yunnan and Guizhou, which can be used to prevent the occurrence of tumors. The extract of SDF (SDFE) is confirmed to be antitumor by pre-experiment. However, effective components and anticancer mechanisms of SDFE are still unclear. Aim of the studyThe purpose of this study was to explore the material basis and action mechanisms of SDFE in the treatment of non-small cell carcinoma (NSCLC). Materials and methodsUHPLC-Q-Exactive-Orbitrap-MS/MS was used to identify the chemical components of SDFE. The network pharmacology was applied to screen out the main active components, core genes and related signaling pathways of SDFE in treatment of NSCLC. Molecular docking was used to predict the affinity of major components and core targets. The database was applied to predict the mRNA and protein expression levels of core targets in NSCLC. Finally, the experiments in vitro were performed by CCK-8, flow cytometry and western blot (WB). ResultsIn this study, 98 chemical components were identified by UHPLC-Q-Exactive- Orbitrap-MS/MS. 5 main active components (namely quercetin, genistein, luteolin, kaempferol, isorhamnetin), 10 core genes (namely TP53, AKT1, STAT3, SRC, MAPK3, EGFR, JUN, EP300, TNF, PIK3R1) and 20 pathways were screened out through network pharmacology. The 5 active ingredients were molecularly docked with the core genes, and most the LibDockScore values were higher than 100. The data collected from the database indicated that TP53, AKT1 and PIK3R1 were closely related to the occurrence of NSCLC. The results of experiment in vitro showed that SDFE promoted NSCLC cells apoptosis by down-regulating the phosphorylation of PI3K, AKT and MDM2, up-regulating the phosphorylation of P53, inhibiting the expression of Bcl-2 and up-regulating the expression of Bax. ConclusionThe combination of network pharmacology, molecular docking, database validation, and in vitro experimental validation effectively demonstrates that SDFE can promote cell apoptosis by regulating PI3K-AKT/MDM2-P53 signaling pathway, so as to treat NSCLC.

#3652 ACUTE KIDNEY INJURY (AKI) IN CANCER PATIENTS TREATED WITH COMBO THERAPIES: CHEMOTHERAPY, OR IMMUNOTHERAPY, THAT IS THE QUESTION

Abstract Background and Aims Lung cancer is the second most common malignancy in men and the third in women and approximately 85% of all cases are constituted by non-small cell carcinoma (NSCLC). In recent years, the introduction of immune checkpoint inhibitors and molecular targeted therapies, as monotherapy or in association with chemotherapy, has revolutionized the treatment of NSCLS. Pembrolizumab in association with pemetrexed and carboplatin, for instance, has been approved as first-line treatment for non-squamous NSCLC. Nephrotoxic side effects of both old and new therapies continue to be a substantial adverse event (AE) and could preclude effective oncological treatment. When a patient in combined oncological therapy develops AKI it is not always easy to establish which drug is responsible of the AE. The objective of our study was to develop a diagnostic algorithm to help the clinician to diagnose and manage AKI in patient treated with pembrolizumab + pemetrexed +/- carboplatin. Method We performed a retrospective multicentric data collection. We analyzed data about all the patient referred to the onconephrology outpatient clinic due to AKI (Stage 2 or higher) during oncological treatment with pembrolizumab + pemetrexed +/- carboplatin, from 2020 to 2022. AKI stages were identified according to KDIGO guidelines and CTCAE 5.0. We focused on the following data: chemical-physical urinalysis, urinary electrolytes, serum electrolytes, kidney function (AKI progression and trend of renal function after oncological drug discontinuation). Results A cohort of 89 patients was analyzed: 54 males (61%) and 35 females (39%), with an average age of 69 years (51-76). The main comorbidities were hypertension (76%), diabetes mellitus (36%), CKD (64%) and cardiovascular diseases (26%). Overall, 11 patients (12%) had a non drug-related AKI, 90% of which due to pre-renal causes. 43 patients developed immune-related AKI; among these 23 pts had sterile pyuria and/or WBC casts, 35 pts had other organ IrAEs, 32 pts had AKI progression upon discontinuation of oncological therapy, and 37 pts had an increase in serum creatinine ≥1 mg/dl between two consecutive pretherapy blood tests. Chemotherapy-induced nephrotoxicity occurred in 35 patients and had the following features: hypo K or hypo Mg in 9 pts, increased urinary electrolytes in 16 pts, stable renal function after oncological drugs discontinuation in 32 pts and an increase in serum creatinine ≤0,5 mg/dl between two consecutive pretherapy blood tests in 27 pts. Characteristics of drug-related AKI are summarized in Table 1. Conclusion One of the main challenges with patients on multiple cancer therapies who develop AKI is to identify the possible drug responsible for the nephrotoxicity to avoid unnecessary suspension of one or more oncological drugs. Although the most frequently suggested approach is the execution of the renal biopsy, it is not always possible to perform it in a short time due to difficulties in organizing the diagnostic procedure and the time necessary for the histological analysis. Furthermore, Oncological Guideline recommend starting steroid therapy as soon as the Grade ≥2 immune related AEs develop. The above retrospective results shed light on the main characteristic of AKI due to immunotherapy or chemotherapy; the information obtained helped us to develop a diagnostic algorithm that addresses the clinician in identifying with reasonable certainty the cause of AKI without the need to perform a renal biopsy (Figure 1).

Correlation of Programmed Death-Ligand 1 Expression With Lung Adenocarcinoma Histologic and Molecular Subgroups in Primary and Metastatic Sites

Programmed death-ligand 1 (PD-L1) expression in terms of the tumor proportion score (TPS) is the main predictive biomarker approved for immunotherapy against lung nonsmall cell carcinoma. Although some studies have explored the associations between histology and PD-L1 expression in pulmonary adenocarcinoma, they have been limited in sample size and/or extent of examined histologic variables, which may have resulted in conflicting information. In this observational retrospective study, we identified primary and metastatic lung adenocarcinoma cases in the span of 5 years and tabulated the detailed histopathologic features, including pathological stage, tumor growth pattern, tumor grade, lymphovascular and pleural invasion, molecular alterations, and the associated PD-L1 expression for each case. Statistical analyses were performed to detect associations between PD-L1 and these features. Among 1658 cases, 643 were primary tumor resections, 751 were primary tumor biopsies, and 264 were metastatic site biopsies or resections. Higher TPS significantly correlated with high-grade growth patterns, grade 3 tumors, higher T and N stage, presence of lymphovascular invasion, and presence of MET and TP53 alterations, whereas lower TPS correlated with lower-grade tumors and presence of EGFR alterations. There was no difference in PD-L1 expression in matched primary and metastases, although higher TPS was observed in metastatic tumors due to the presence of high-grade patterns in these specimens. TPS showed a strong association with a histologic pattern. Higher-grade tumors had higher TPS, which is also associated with more aggressive histologic features. Tumor grade should be kept in mind when selecting cases and blocks for PD-L1 testing.

The use of minimal residual disease in thoracic oncology: Gaps between promises and the on-the-ground reality of daily practice.

The assessment of minimal residual disease (MRD) from blood samples of patients with resected non-small cell lung carcinoma (NSCLC) is promising and opens up many opportunities for the optimisation of patient care in daily practice. Notably, this includes the potential for escalation or de-escalation of adjuvant therapies. Thus, the evaluation of MRD status can directly contribute to an increase in the overall survival of early stage NSCLC patients and/or limit therapeutic but also "financial" toxicity. Therefore, several clinical trials recently evaluated MRD in early stage NSCLC by integrating and retrospectively comparing the results of MRD assessments. In this context, there is an urgent need to close the gap between clinical research and the use of the evaluation of MRD in routine daily practice. Further action needs to be taken, particularly in evaluating the pertinence of the detection of MRD in prospective interventional clinical studies. This may be done in part by comparing different parameters, such as the techniques used, the different time points and the cutoffs of MRD assessments. This article investigates the assessment of MRD in non-small cell lung cancers, with a special focus on the issues associated with the various assays and the limitations of using circulating free DNA analyses for MRD assessment in early stage lung cancer. Recommendations and tips for the optimisation of MRD evaluation in non-small cell lung cancers are provided.

The Role of Immunotherapy or Immuno-Chemotherapy in Non-Small Cell Lung Cancer: A Comprehensive Review.

Many new treatment modalities for non-small-cell carcinoma (NSCLC) have been described in the last two decades. Surgical resections remain the gold standard for early stages and may be considered for locally advanced tumors. Medical treatment has changed drastically in recent years, especially for advanced stages, for which the development of immunotherapy and molecular targeted therapy significantly increased survival and quality of life. The addition of radical surgical resection following immunotherapy or immuno-chemotherapy is feasible and safe with low surgical-related mortality and morbidity in selected patients with initially unresectable NSCLC. However, data from multiple ongoing trials with overall survival as the primary endpoint should be awaited before this strategy is introduced into the standard of care.

Two Cases of Anti-PD1 Antibody Associated Neurological Immune-Related Adverse Effects (P5-4.001)

<h3>Objective:</h3> We present two cases of neurological immune-related adverse events (irAEs) indefinitely triggered by pembrolizumab. <h3>Background:</h3> Recently, immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy. Programmed cell death protein 1 (PD-1) is a key immune checkpoint receptor expressed by activated T cells. PD-1/PD-L1 antibody therapy is used to treat multiple malignancies; however, it has been associated with an increasing number of irAEs. Neurological irAEs are highly significant complications of ICI therapy that can cause long-term disability and death. Most commonly, neurological irAEs are neuromuscular complications and occur within 4 months after immunotherapy initiation. The anti-PD-1 agent pembrolizumab is currently approved for treatment of several tumors and has been used increasingly due to its more favorable toxicity profile. <h3>Design/Methods:</h3> NA <h3>Results:</h3> NA <h3>Conclusions:</h3> <h3>Case 1:</h3> Our first case is an 84-year-old man with a history of metastatic colon cancer that was treated with pembrolizumab. This is thought to have elicited myositis with elevated CK as well as acetylcholine receptor antibody-positive myasthenia gravis, causing him diffuse and debilitating weakness and functional limitation. He had multiple exacerbations of these symptoms temporally associated with pembrolizumab administration. With the initiation of maintenance treatment and the cessation of pembrolizumab, he required no further admissions for neurologic irAEs, but ultimately he was transitioned to hospice care for cancer progression. <h3>Case 2:</h3> A 65-year-old man with a history of non-small cell carcinoma of the lung on pembrolizumab and zoledronic acid presented with altered mental status and agitation. He had mild pleocytosis on CSF, MRI brain with left mesial temporal T2 FLAIR hyperintensity and nonspecific encephalopathy markers on continuous EEG. He subsequently had complete recovery with IV high-dose steroids followed by plasmapheresis. His symptoms were therefore suspected to be secondary to autoimmune encephalitis elicited by pembrolizumab administration. His oncologist elected to transition to another treatment regimen, and he has had no relapses to date. <b>Disclosure:</b> Ms. Vitek has nothing to disclose. Dr. Hansra has nothing to disclose.

Abstract 2928: TROP2 ProTriTAC™, a protease-activated T cell engager prodrug targeting TROP2 for the treatment of solid tumors

Abstract Tumor-associated calcium signal transducer 2 (Trop2) is a cell surface glycoprotein that promotes cell renewal, proliferation and tumorigenesis. Trop2 is homogenously overexpressed in numerous solid tumor types, including breast, head and neck, prostate, bladder, and non-small cell carcinoma; however, Trop2 is also expressed in several normal tissues, including skin, respiratory tract, and female reproductive organs. Although Trop2-targeted antibody drug conjugates (ADCs) have demonstrated clinical activity, with regulatory approvals in subsets of breast and bladder cancers, their broader utility is still hampered by off-target payload-mediated toxicities. To address this issue, and to avoid on-target off-tumor toxicities, we developed a Trop2-targeting ProTriTAC™ (Protease-activated Tri-specific T cell Activating Construct), a T cell engager prodrug which is engineered to be preferentially activated in tumor tissue. ProTriTACs consists of three humanized antibody-derived binding domains on a single polypeptide chain: anti-albumin for half-life extension, anti-CD3 for T cell engagement, and anti-target antigen for tumor cell engagement. The anti-albumin domain, bearing a masking moiety and a protease-cleavable linker, keeps the prodrug inert by inhibiting binding of the adjacent anti-CD3 domain to T cells. Cleavage of the linker by tumor-associated proteases removes the anti-albumin domain along with the masking moiety to reveal a potent active drug that directs T cell killing within the tumor. As designed, in vitro binding and functional assays show that the protease-activated T cell engager has &amp;gt;1000-fold improved binding to primary human T cells and ~100-fold improved T cell killing compared to its intact masked prodrug. In immunodeficient mice reconstituted with human T cells, anti-Trop2 ProTriTAC demonstrated robust anti-tumor activity in multiple xenograft tumor models, including HCC70 (breast), CAL27 (head and neck), and HPAFII (pancreatic), with complete tumor regression as low as 30 μg/kg. To determine the potential toxicity and toxicokinetic characteristics of anti-Trop2 ProTriTAC, an intra-animal dose escalation was conducted in cynomolgus monkeys until individual maximum tolerated dose (MTD). The starting dose was 20 μg/kg with weekly 3-fold dose escalations until MTD. The one-month study revealed that anti-Trop2 ProTriTAC was tolerated at the 180 μg/kg dose level, but not at the next higher dose level of 540 μg/kg. Toxicokinetics, gross pathology, histopathology, and cytokine data will be presented. The preclinical activity in rodent tumor models, coupled to its tolerability in cynomolgus monkeys, support the development of anti-Trop2 ProTriTAC as a therapeutic in a broad range of Trop2-expressing solid tumors. Citation Format: Sony S. Rocha, Regina Lin, Maria R. Dayao, Raphaela Rose Banzon, Subramanian Thothathri, Kevin J. Wright, Wade Aaron, Yinghua Xiao, Nick Bergo, Linh To, Mabel Bush, Manasi Barath, Timothy Yu, Willis Kwong, Hubert Situ, Eric Bragg, Jessica O'Rear, Kevin Carlin, Stephen Yu, Maritza Solorio, Bryan Lemon, Richard Austin, Holger Wesche, S. Jack Lin. TROP2 ProTriTAC™, a protease-activated T cell engager prodrug targeting TROP2 for the treatment of solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2928.

Diagnostic and Prognostic Significance of Serum Biomarkers - Serum Amyloid A and CYFRA 21-1 in Lung Cancer.

Bronchogenic carcinoma is a leading cause of cancer-related death in men and women. Early diagnosis and treatment in these cases are essential for a better prognosis. Serum biomarkers such as serum amyloid A (SAA) and CYFRA 21-1 have generated encouraging results regarding their use in the diagnosis of these cases but data on their role in the Indian scenario are still lacking. The study aims to measure the levels of SAA and CYFRA 21-1 in various types of lung cancer and compare them with patients without lung cancer. It also aims to compare the values of these biomarkers before and after chemotherapy and correlate them with response to treatment. It was a prospective, case-control study conducted in the Department of Pulmonary Medicine, Government Medical College, Chandigarh. All histologically and/or cytologically proven lung cancer cases were included in the study group while patients with diseases other than lung cancer formed the control group. All patients were evaluated through a complete history and thorough clinical examination. Measurement of SAA and CYFRA 21-1 in blood was done by sandwich ELISA method. The patients in the study group were followed up regularly and the biomarkers were measured again after four cycles of chemotherapy. The response of tumors to chemotherapy was evaluated as per modified Response Evaluation Criteria in Solid Tumors criteria. The statistical analysis was carried out using SPSS version 19.0. The study group and control group included 20 patients each. Hoarseness of voice and hemoptysis were significantly associated with lung cancer patients (P = 0.001 and P = 0.025, respectively). Serum levels above 8745 ng/ml for SAA and 2.55 ng/ml for serum CYFRA 21-1 were used as diagnostic biomarker in lung cancer. The serum levels of CYFRA 21-1 were found to be significantly raised in nonsmall cell carcinoma (NSCLC) in comparison to SCLC of lung. There was a statistically significant decrease in the serum levels of CYFRA 21-1 in lung cancer patients on C4 cycle of chemotherapy in comparison to C1 cycle (P = 0.014). SAA and CYFRA 21-1 could be valuable diagnostic biomarkers in lung cancer. CYFRA 21-1, in addition, could also be used as prognostic biomarker in lung cancer patients undergoing chemotherapy as it showed significant decrease after C4-cycle of chemotherapy. It can also be a potential biomarker to differentiate small cell and NSCLC.

Ability of single anesthesia for combined robotic-assisted bronchoscopy and surgical lobectomy to reduce time between detection and treatment in stage I non–small cell lung cancer

Background Background: Early identification, diagnosis, and treatment of lung cancer is associated with improved clinical outcomes. Robotic-assisted bronchoscopy improves the ability to diagnose early stage lung malignancies and, when combined with robotic-assisted lobectomy under single anesthesia, could reduce time from identification to intervention in early stage lung cancer in a select patient population. Methods Methods: A retrospective case-control single-center study compared patients with radiographic stage I non–small cell carcinoma (NSCCA) undergoing robotic navigational bronchoscopy and surgical resection (N = 22) with historical controls (N = 63). The primary outcome was time from initial radiographic identification of a pulmonary nodule to therapeutic intervention. Secondary outcomes included times between identification to biopsy, biopsy to surgery, and procedural complications. Results Results: Patients with suspected stage I NSCCA who received single anesthesia for diagnosis and intervention with robotic-assisted bronchoscopy and robotic-assisted lobectomy had shorter times between identification of a pulmonary nodule and intervention compared to controls (65 vs 116 days, P = 0.005). Cases had lower rates of complications (0% vs 5%) and shorter hospitalizations after surgery (3.6 vs 6.2 days, P = 0.017). Conclusion Conclusion: Our findings support that implementing a multidisciplinary thoracic oncology team and single-anesthesia biopsy-to-surgery approach in management of stage I NSCCA significantly reduced times from identification to intervention, biopsy to intervention, and length of hospital stays in management of lung cancer.

Ligneous brochitis: A clinicopathological correlation of seven cases

Seven patients with ligneous lesions of the bronchus are presented. The patients are five men and two women between the ages of 51 and 79 years (average: 65) who had prior history of pulmonary non-small cell carcinoma in the past 2–3 years. All the patients had undergone surgical resection followed by chemotherapy. The patients were evaluated for the potential recurrence of carcinoma and bronchial biopsies were obtained. Histologically, all the cases shared similar features, manly the presence of a subepithelial amorphous, acellular, eosinophilic material with minimal inflammatory reaction. Special histochemical stains for micro-organisms were negative as well as congo red for the presence of amyloid. No evidence of malignancy was seen in any of the biopsies. The current cases, represent an unusual histological feature that is more in keeping with ligneous bronchitis, possibly secondary to treatment.

Outcomes after sublobar resection versus lobectomy in non-small cell carcinoma in situ.

Guidelines for treatment of non-small cell lung cancer identify patients with tumors ≤2cm and pure carcinoma in situ histology as candidates for sublobar resection. Although the merits of lobectomy, sublobar resection, and lymphoid (LN) sampling, have been investigated in early-stage non-small cell lung cancer, evaluation of these modalities in patients with IS disease can provide meaningful clinical information. This study aims to compare these operations and their relationship with regional LN sampling in this population. The National Cancer Database was used to identify patients diagnosed with non-small cell lung cancer clinical Tis N0 M0 with a tumor size ≤2cm from 2004 to 2017. The χ2 tests were used to examine subgroup differences by type of surgery. Kaplan-Meier method and Cox proportional hazard model were used to compare overall survival. Of 707 patients, 56.7% (401 out of 707) underwent sublobar resection and 43.3% (306 out of 707) underwent lobectomy. There was no difference in 5-year overall survival in the sublobar resection group (85.1%) compared with the lobectomy group (88.9%; P=.341). Multivariable survival analyses showed no difference in overall survival (hazard ratio, 1.044; P=.885) in the treatment groups. LN sampling was performed in 50.9% of patients treated with sublobar resection. In this group, LN sampling was not associated with improved survival (84.9% vs 85.0%; P=.741). We observed no difference in overall survival between sublobar resection and lobectomy in patients with cTis N0 M0 non-small cell lung cancer with tumors ≤2cm. Sublobar resection may be an appropriate surgical option for this population. LN sampling was not associated with improved survival in patients treated with sublobar resection.

Selinexor demonstrates anti-tumor efficacy in paired patient-derived xenograft models and hydrogel-embedded histoculture drug sensitivity test of penile cancer.

Penile cancer is a rare malignancy with a poor prognosis, even with various treatment options. Considering the little progress in the study of the pathogenesis and treatment of penile cancer because of the lack of models that mimic the biological properties of the tumor, we have developed a patient-derived xenograft (PDX) model and paired hydrogel-embedded histoculture drug sensitivity test (HDST) to screen for drugs that can inhibit tumors. The increased expression of XPO1, as a key nuclear export protein involved in the transport of various tumor suppressors and cell cycle regulatory proteins, is associated with the prognosis of a variety of tumors [World J Uroly 27(2):141-150, 2009]. Selinexor is an inhibitor of XPO1, which can treat cancers, such as multiple myeloma, gastric cancer, triple-negative breast cancer, and non-small cell carcinoma [Transl Androl Urol 6(5):785-790, 2017; OncoTargets Therapy 13:6405-6416, 2020]. However, whether XPO1 inhibition has a role in penile cancer remains unknown. Therefore, this article used the PDX and HDST models to investigate whether the inhibition of XPO1 has an effect on penile cancer and its underlying mechanism. We used penile cancer tumor tissues to construct a PDX model of penile cancer and paired PDXE model and confirmed the consistency of PDX tumor tissues in source patients. Then, we assessed the ability of Selinexor to inhibit penile cancer tissues in vivo using a PDX model and in vitro by HDST. We also examined the potential mechanism of XPO1 action on penile cancer by IHC and TUNEL. Finally, we assessed the safety of the drug treatment by H&E and biochemical blood analysis. Result showed that the penile cancer PDX model and patient penile cancer tissues were clinically consistent in morphological characteristics and protein expression. In addition, Selinexor could inhibit tumor growth in PDX models and HDST. We found that P53, P21 expression was upregulated; Cyclin D1 expression was downregulated, and apoptosis of tumor cells was increased in the Selinexor-treated PDX model. Moreover, it had no significant effect on liver, kidney, and cardiac function. The PDX model of penile cancer was a powerful tool for penile cancer research and new drug development. It showed that Selinexor can effectively inhibit penile cancer in vitro and in vivo. In addition, XPO1 may affect P53, P21, and Cyclin D1 expression to regulate the growth and apoptosis of penile carcinoma.

Endobronchial ultrasound bronchoscopy Franseen fine needle biopsy tool versus standard fine needle aspiration needle: Impact on diagnosis and tissue adequacy

BackgroundThe Franseen fine needle biopsy tool (Acquire®, Boston Scientific, Boston, MA) may provide better quality specimens than current endobronchial ultrasound-transbronchial needle aspiration (EBUS-TNBA) needles. We performed a comparative retrospective study evaluating the diagnostic yield of the Franseen fine needle biopsy (FNB) versus standard fine needle aspiration (FNA) for benign lymphadenopathy and tissue acquisition for next generation sequencing (NGS) in non-small cell carcinoma (NSCLC). MethodsAll EBUS-TBNA procedures performed between January 1st, 2019 to January 1st, 2020 where both the FNB needle and the FNA needle were used were analyzed. All demographic, procedural, and diagnostic data were recorded. The median tumor surface area, tumor cellularity and adequacy for NGS was evaluated for NSCLC specimens. ResultsA total of 69 target lesions in 66 patients were biopsied with both the FNB and FNA needles. The mean (SD) size of target biopsied was 1.8 cm (0.8); The most common stations were 7 (54%) and 4R (26%). The mean (SD) needle passes were 6 (2.2) and 4 (1.8) with FNA and FNB needles, respectively (p < 0.0001). Benign lymphadenopathy was diagnosed with FNA needle in 46% and in 82% with FNB (p < 0.0001). NGS tissue adequacy was 47% with FNA needle versus 76% with FNB (p = 0.02). Median tumor surface area and tumor cellularity were greater with FNB needle than FNA needle (80 mm2 versus 9 mm2, p = 0.002, and 81% versus 45%, p = 0.0004). ConclusionThe FNB needle demonstrated higher diagnostic yield in benign lymphadenopathy and higher quality for NGS than standard FNA needle.