Non-small Cell Carcinoma Research Articles

Pan-Canadian cohort of immune checkpoint inhibitor-induced insulin-dependent diabetes mellitus (CANDIED).

2640 Background: Endocrine immune-related adverse events (irAEs) are frequent with immune checkpoint inhibitors (ICIs); however, ICI-related insulin-dependent diabetes mellitus (IDDM) is a rare but serious endocrine irAE. We describe the characteristics of patients who developed ICI-related IDDM across five academic Canadian cancer centres. Methods: In this multicentre, retrospective study, we included both patients who developed IDDM and patients with non-IDDM (NIDDM) or pre-DM who became insulin-dependent while on treatment with ICI. We collected data on primary tumor type, ICI regimen (single agent or combination), time to development of IDDM from ICI initiation, comorbidities, laboratory parameters at the time of IDDM diagnosis, tumor response and survival. A p value < 0.05 was considered statistically significant. Results: We identified 27 patients between July 2016 and August 2019. Median age was 60 (39-79) years, 20 (74%) were male, 15 (55%) had melanoma and 4 each (15%) non-small cell lung cancer (NSCLC) and renal cell carcinoma. Seven (26%) patients had prior NIDDM or pre-DM; 5 (18%) had an auto-immune disease (2 psoriasis, 2 inflammatory bowel disease, and 1 systemic lupus erythematosus). Laboratory parameters at presentation and management of IDDM are presented in the Table. Mean A1c was not statistically different between patients with or without prior NIDDM or pre-DM (8.4% vs. 8.6%; p = 0.9). All IDDM events were irreversible; 1 (4%) patient died of diabetic ketoacidosis. At time of IDDM diagnosis, 17 (63%) patients were receiving single agent anti-PD1 and 10 (37%) anti-PD1-based combinations (7 anti-CTLA-4, and 3 other compounds). Median time for development of IDDM from ICI initiation was 2.7 months (95% CI 0.2-5.3). Patients receiving combination ICI developed IDDM earlier than those treated with single agent (1.4 vs 4.8 months; p = 0.05). Amongst patients with metastatic disease (n = 24), 9 (38%) had a complete response and 7 (29%) had a partial response. Two patients (8%) were treated in the adjuvant setting; 1 (4%) received consolidation ICI. IDDM led to ICI discontinuation in 12 (44%) patients. After a median follow up of 21 months from ICI initiation, median survival was 30 months (95% CI NE) and was not reached in patients with melanoma and NSCLC. Conclusions: ICI-related IDDM is a rare and typically irreversible irAE that occurs early in the course of treatment and develops earlier with combination ICI. In this cohort, patients who developed ICI-related IDDM had a high tumor response rate and prolonged survival, especially melanoma and NSCLC patients. Prospective evaluation of autoantibodies to predict development of IDDM is ongoing.[Table: see text]

A Case of Paraneoplastic Cushing’s Syndrome in Recurrent Squamous Cell Carcinoma

Abstract Background: Ectopic production of ACTH causing Cushing’s syndrome (CS) is rare but has been well described in association with bronchial carcinoids, thymomas, pancreatic malignancies, and small cell lung carcinomas. We report a rare case of CS caused by ACTH-producing non-small cell carcinoma. Clinical Case: A 71 year-old man with a history of squamous cell carcinoma of the lung (T2bN1M0) 10 years prior who underwent lobectomy and adjunctive chemotherapy, presented with a new cough, weight loss, and bilateral lower extremity edema. He was also noted to have significant fatigue, hypertension, symptomatic hyperglycemia, and hypokalemia. CT chest revealed a large right perihilar mass with mediastinal adenopathy and numerous hepatic lesions. A biopsy of the liver lesions revealed a poorly differentiated carcinoma with neuroendocrine features strongly positive for AE1/3 with focal p40+, CK7, synaptophysin, chromogranin, and TTF1. It was negative for p63, CK5/6, CDX2, CK20, and GATA3. The morphology and immunohistochemical staining favored a squamous primary. Unfortunately, there was insufficient tissue sample to stain for ACTH. Biochemical evaluation revealed: post-1 mg dexamethasone serum cortisol 74.8 µg/dL (N < 1.8 µg/dL), 24 hr urine free cortisol 2987 µg/g creatinine (normal: < 32 µg/g creatinine), and ACTH 170 pg/mL (N < 47 pg/mL). Other notable findings at presentation were potassium 2.8 mmol/L (N: 3.7-5.1 mmol/L) and glucose 371 mg/dL (N: 74-99 mg/dL). MRI brain revealed focal pituitary infundibular thickening up to 6 mm in diameter and an enlargement of the pituitary gland concerning for metastasis. The patient’s clinical course was complicated by persistent hypokalemia and hyperglycemia which were treated with spironolactone 100 mg twice a day and insulin therapy, respectively. Ketoconazole 100 mg twice a day was initiated for the hypercortisolemia; etoposide, carboplatin, and atezolizumab were started for the neuroendocrine tumor. The patient expired due to sepsis one month after the diagnosis of Cushing’s syndrome. Conclusion: We report a rare case of paraneoplastic Cushing’s syndrome due to poorly differentiated neuroendocrine tumor with a squamous cell carcinoma primary. ACTH producing non-small cell carcinomas have been seldom reported in the literature. Although we were unable to provide ACTH staining on pathology, the existence of an obvious neuroendocrine tumor, marked elevation in ACTH, and an MRI which was negative for a pituitary adenoma, strongly suggests paraneoplastic Cushing’s syndrome.

Next-Generation Sequencing with Liquid Biopsies from Treatment-Naïve Non-Small Cell Lung Carcinoma Patients.

Simple SummaryScreening for genomic alterations in treatment-naïve non-small cell lung carcinoma (NSCLC) is mainly done by tissue biopsy (TB), an invasive approach. However, it may not be possible to obtain a TB, the patient does not consent to it and/or the extracted nucleic acids are of poor quantity and/or quality for further genomic analyses, so a liquid biopsy (LB) is the only option to detect molecular target(s) for first-line treatment in these patients. However, a LB at diagnosis is still not often used in clinical centers since a TB is currently the gold standard approach for histological diagnosis, assessment of the PD-L1 status on tumor cells and evaluation of the molecular alterations. A number of different approaches are already available for the assessment of genetic abnormalities with LB, but next-generation sequencing (NGS) is the most promising. This review provides an overview of the main studies currently using LB NGS at diagnosis for NSCLC. We discuss its advantages and limitations in comparison with a TB and the perspectives for the future.Recently, the liquid biopsy (LB), a non-invasive and easy to repeat approach, has started to compete with the tissue biopsy (TB) for detection of targets for administration of therapeutic strategies for patients with advanced stages of lung cancer at tumor progression. A LB at diagnosis of late stage non-small cell lung carcinoma (NSCLC) is also being performed. It may be asked if a LB can be complementary (according to the clinical presentation or systematics) or even an alternative to a TB for treatment-naïve advanced NSCLC patients. Nucleic acid analysis with a TB by next-generation sequencing (NGS) is gradually replacing targeted sequencing methods for assessment of genomic alterations in lung cancer patients with tumor progression, but also at baseline. However, LB is still not often used in daily practice for NGS. This review addresses different aspects relating to the use of LB for NGS at diagnosis in advanced NSCLC, including its advantages and limitations.

Circulating Biomarkers for Early Stage Non-Small Cell Lung Carcinoma Detection: Supplementation to Low‐Dose Computed Tomography

Lung cancer is currently the leading cause of cancer death in both developing and developed countries. Given that lung cancer has poor prognosis in later stages, it is essential to achieve an early diagnosis to maximize patients’ overall survival. Non-small cell lung cancer (NSCLC) is the most common form of primary lung cancer in both smokers and non-smokers. The current standard screening method, low‐dose computed tomography (LDCT), is the only radiological method that demonstrates to have mortality benefits across multiple large randomized clinical trials (RCT). However, these RCTs also found LDCT to have a significant false positive rate that results in unnecessary invasive biopsies being performed. Due to the lack of both sensitive and specific screening methods for the early detection of lung cancer, there is an urgent need for alternative minimally or non-invasive biomarkers that may provide diagnostic, and/or prognostic information. This has led to the identification of circulating biomarkers that can be readily detectable in blood and have been extensively studied as prognosis markers. Circulating microRNA (miRNA) in particular has been investigated for these purposes as an augmentation to LDCT, or as direct diagnosis of lung cancer. There is, however, a lack of consensus across the studies on which miRNAs are the most clinically useful. Besides miRNA, other potential circulating biomarkers include circulating tumor cells (CTCs), circulating tumor DNA (ctDNAs) and non-coding RNAs (ncRNAs). In this review, we provide the current outlook of several of these biomarkers for the early diagnosis of NSCLC.

Clinicopathological characteristics and survival outcomes in neuroendocrine prostate cancer: A population-based study.

Objective:This study aimed to investigate the clinicopathological features and the survival outcomes of neuroendocrine prostate cancer (NEPC).Methods:Within the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute, we identified a total of 510 patients with NEPC between 2006 and 2015. Age-adjusted incidence rates were evaluated in the study by the SEER∗Stat Software version 8.3.6. Kaplan–Meier analysed assessed overall survival (OS) after stratification according to marital status, age, histologic subtype, metastatic status, and treatment. The significant differences were assessed in a log-rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS.Results:From a total of 560,124 patients with prostate cancer diagnosed between 2006 and 2015, we identified 510 cases of de novo NEPC. Regarding histology, among all the NEPC, 329 (64.5%) patients were diagnosed as small cell carcinoma, 181 (39.8%) were nonsmall cell carcinoma. The overall age-adjusted incidence of NEPC statistically significantly increased from 0.321/1,000,000 person-years in 2006 to 0.587/1,000,000 person-years in 2015. The median OS in our study cohort was 9 months (95% CI, 8–10 months). Multivariate cox regression analysis showed that age, histologic subtype, and stage were independent prognostic factors for NEPC patients. The majority of NEPC (78.2%) were metastatic at diagnosis. In terms of treatment, for metastatic tumor patients, chemotherapy was the most effective therapy. Chemotherapy increased the OS of patients with regional (distant) metastases from 8 months (5 months) to 13.5 months (9 months).Conclusion:NEPC is extremely rare but the incidence of NEPC has been increasing in the past years. The prognosis of NEPC is poor because most cases are diagnosed at metastatic stage. The patients with metastases are typically treated with chemotherapy and chemotherapy shows survival benefits in both regional and distant metastatic tumor patients.

The value of combined detection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the differential diagnosis of lung cancer.

BackgroundTo investigate the value of carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), squamous cell carcinoma antigen (SCC-Ag), and gastrin-releasing peptide (pro-GRP) in the differential diagnosis of lung cancer.MethodsWe enrolled 120 patients with malignant lung cancer who were treated at our hospital between June 2018 to June 2020. A further 58 patients with benign lung tumors and 60 healthy volunteers were also enrolled. Serum levels of CEA, CYFRA21-1, SCC-Ag, and pro-GRP were determined and compared across different populations, different pathological types, and different TNM stages. An ROC curve was drawn to evaluate the value of the four indicators when combined for the diagnosis of lung cancer.ResultsThe levels of CEA, CYFRA21-1, SCC-Ag, and pro-GRP in the malignant group were significantly higher than those in the benign and healthy groups (P<0.05). CEA in adenocarcinoma was significantly higher than that in squamous cell carcinoma (SCC) and small cell carcinoma (P>0.05), and CYFRA21-1 in non-small cell carcinoma was significantly higher than that in small cell carcinoma (P<0.05). Pro-GRP in small cell carcinoma was significantly higher than that in non-small cell carcinoma (P<0.05), and the SCC-Ag level in SCC was significantly higher than that in small cell carcinoma and adenocarcinoma (P<0.05). There was no statistically significant difference in CEA among various pathological types (P>0.05). However, there were significant differences in the levels of CEA and pro-GRP in different TMN stages (P<0.05), and in the levels of CEA and pro-GRP in different TMN stages (P<0.05) where from stage I to stage IV CEA, pro -GRP levels increased. There was a significant difference in CYFRA21-1 levels in stages I–III (P<0.05), and in stages III and IV, although there was no statistically significant difference in SCC-Ag in different stages (P>0.05). The area under the curve (AUC) for the combined diagnosis of lung cancer with the four markers was 0.9250 (95% CI: 0.8866-0.9634), the sensitivity was 93.29%, and the specificity was 84.32%.ConclusionsJoint inspection of CEA, CYFRA21-1, SCC-Ag, and pro-GRP levels has certain clinical value for the differential diagnosis of lung cancer.

Extended Segmentectomy for Small Lung Nodule with Image-Guided Video-Assisted Thoracoscopic Surgery

Patients with clinical T1aN0M0 Non-Small Cell Carcinoma (NSCLC) or poor pulmonary function may benefit more from segmentectomy compared to lobectomy. However, there is question about segmentectomy provides not enough safe margin, especially for nodules situated at the intersegmental area. We describe a novel technique using image-guided Video-Assisted Thoracoscopic Surgery (iVATS) to accomplish extended segmentectomy for central lung nodules. This technique helps to overcome the challenges of nodules situated at the intersegmental area.

175P Incidence and treatment outcomes of brain metastasis in advanced non-small cell lung cancer at presentation: An experience from south India

Background: Brain metastasis is one of the significant problems in patients with lung cancer. Most of the patients are asymptomatic at presentation. Prognosis and survival in these patients are lacking. Many studies that looked upon the incidence of brain metastasis at the presentation of NSCLC are retrospective. In India, brain metastasis frequency in patients with NSCLC at the presentation has not been well studied. This study has been planned to evaluate the incidence of brain metastasis in NSCLC patients treated in our center. Methods: It is a prospective observational study conducted in medical oncology at our tertiary care center from Sep 2019- Sep 2020. A total of 150 patients with lung cancer were registered in the department. Among them, 112 patients had advanced non-small cell carcinoma of the lung (NSCLC), and they were enrolled in the study. MRI brain was taken at the time of diagnosis. Results: The mean age at presentation was 60 years. The Median follow-up was 15 months. Median overall survival in the study was 11 months. Patients with brain metastasis had a median survival of 7 months, whereas patients without brain metastasis had 13 months. Clinical profile, performance status, demographic characteristics, and imaging findings were noted at the presentation time and the results were analyzed as follows. Table 175PBaseline characteristicsNo of Patients (%)Mean age60 years<6044 (39%)>6068 (61%)SexMale69 (62%)Female43 (38%)Adenocarcinoma86 (77%)Squamous cell carcinoma26 (23%)Brain metastasis39 (35%)Male19 (49%)Female20 (51%)Adenocarcinoma32 (82%)Squamous cell carcinoma7 (18%)Asymptomatic12 (30%)Symptomatic27 (70%)Synchronous metastasis21 (19%)Contralateral lung metastasis12 (57%)Bone metastasis5 (23%) Open table in a new tab Conclusions: The study period is short, so that data on molecular abnormalities in patients with brain metastasis was not included in the data. Our study found that female patients were at higher risk for brain metastasis. Other risk factors were adenocarcinoma histology and age less than 60 years. There are no biomarkers to predict brain metastasis in NSCLC due to its molecular heterogeneity. The study will serve as a baseline platform of clinical predictors of brain metastasis in NSCLC. Our future direction and research will be clinical predictors along with molecular driver mutations in NSCLC in detecting brain metastasis. Legal entity responsible for the study: Rajiv Gandhi Government General Hospital, Madras Medical College. Funding: Has not received any funding. Disclosure: The author has declared no conflicts of interest.

Diffusion Tensor Imaging Can Discriminate the Primary Cell Type of Intracranial Metastases for Patients with Lung Cancer.

Purpose: Histopathological differentiation of primary lung cancer is clinically important. We aimed to investigate whether diffusion tensor imaging (DTI) parameters of metastatic brain lesions could predict the histopathological types of the primary lung cancer.Methods: In total, 53 patients with 98 solid metastatic brain lesions of lung cancer were included. Lung tumors were subgrouped as non-small cell carcinoma (NSCLC) (n = 34) and small cell carcinoma (SCLC) (n = 19). Apparent diffusion coefficient (ADC) and Fractional anisotropy (FA) values were calculated from solid enhanced part of the brain metastases. The association between FA and ADC values and histopathological subtype of the primary tumor was investigated.Results: The mean ADC and FA values obtained from the solid part of the brain metastases of SCLC were significantly lower than the NSCLC metastases (P < 0.001 and P = 0.003, respectively). ROC curve analysis showed diagnostic performance for mean ADC values (AUC=0.889, P = < 0.001) and FA values (AUC = 0.677, P = 0.002). Cut-off value of > 0.909 × 10-3 mm2/s for mean ADC (Sensitivity = 80.3, Specificity = 83.8, PPV = 89.1, NPV = 72.1) and > 0.139 for FA values (Sensitivity = 80.3, Specificity = 54.1, PPV = 74.2, NPV= 62.5) revealed in differentiating NSCLC from NSCLC.Conclusion: DTI parameters of brain metastasis can discriminate SCLC and NSCLC. ADC and FA values of metastatic brain lesions due to the lung cancer may be an important tool to differentiate histopathological subgroups. DTI may guide clinicians for the management of intracranial metastatic lesions of lung cancer.

P01.22 Outcomes in NSCLC Patients with Early Termination of Immune Checkpoint Inhibitors Due to Toxicities

Immune checkpoint inhibitors (ICIs) have improved outcomes of patients with advanced non-small cell carcinoma (NSCLC). There is no consensus on the maximum duration of ICIs in metastatic disease. Immune related adverse events (IRAEs) with ICIs, although rare, can have serious and life-long consequences. We aim to describe the real-world data on outcomes of NSCLC patients who stopped ICIs earlier than proposed duration due to IRAEs. Patients with stage III or IV NSCLC treated with ICIs at Monash Health (Melbourne, Australia) from 2015 to 2019 were retrospectively reviewed. Patients enrolled to clinical trials were excluded. Baseline clinicopathological factors and anti-cancer treatment details were collected. Immunohistochemistry for PD-L1 staining was performed and scored according to standardised practice. IRAEs and reason for ICI cessation was recorded. Overall survival (OS) from the start of ICI was calculated using Kaplan-Meier method. A total of 148 patients received ICI therapy with 97 male (66%) and 51 female (34%) patients. 91% were smokers and ECOG 0 or 1 was found in 95%. PD-L1 expression was known in 53/148 patients; where 19% were scored as low, 43% as intermediate and 20% as high. Stage at commencement of ICI was III in 36/148 (24%), where 32/36 (89%) received adjuvant durvalumab after curative intent chemoradiotherapy, and metastatic in 112/148 (76%), where 99 (88%) received nivolumab and 13 (12%) received pembrolizumab, after first line chemotherapy. Median doses of ICIs were 17 in stage III, and 7 in stage IV cohorts. ICIs were ceased in 93/148 (63%) cases due to disease progression, while 38/148 (26%) stopped due to IRAEs; 17 (12%) in stage III and 21 (14%) in stage IV cohort. Severe IRAEs (grade 3 or higher) were pneumonitis (7/148, 5%), colitis (4/148, 3%), endocrinopathy (2/148, 1%), arthritis (2/148, 1%), rash (2/148, 1%) cardiac (2/148, 1%), liver (1/148, 1%), optic neuritis (1/148, 1%), thrombocytopenia (1/148, 1%; grade 5, death). Median OS (mOS) was 29.7 months (range 0.57 – 40.5) in stage III disease and 9.4 months (range 0.37 – 58.1) in stage IV disease. mOS in patients stopping ICI due to disease progression was 8.16 months, while it was 32.43 months in patients stopping earlier due to toxicities, (N/R in patients receiving durvalumab; and 32.43 months in those receiving nivolumab or pembrolizumab). Only 2/112 (2%) patients with stage IV disease completed a minimum of 2 years of ICI treatment, while only 8/36 (22%) completed the recommended 12 months of durvalumab in the stage III cohort. PD-L1 status did not predict survival (p=0.99). Significant number of patients terminated ICIs due to toxicities without progression of their disease. However, this early termination did not result in inferior survival. Exploring strategies involving early stopping of ICIs at maximum tumour response and restarting at progression may have useful clinical value in preventing serious IRAEs.

Prognostic Impact of Albumin-bilirubin (ALBI) Grade on Non-small Lung Cell Carcinoma: A Propensity-score Matched Analysis.

Albumin-bilirubin (ALBI) grade is an indicator of liver dysfunction and is useful for predicting postoperative prognosis of hepatocellular carcinomas. However, the significance of ALBI grade in non-small cell lung carcinoma (NSCLC) has not been elucidated. We analyzed 947 patients with pStage IA-IIIA NSCLC. We divided patients into ALBI grade 1 and grade 2/3 groups. We then analyzed the association of ABLI grade with clinicopathological characteristics and prognosis in NSCLC by using propensity-score matching. ALBI grade 2/3 was significantly associated with older age, male sex, advanced pT status, and histological type. Even after propensity-score matching, ALBI grade 2/3 patients had significantly worse cancer-specific survival (CSS) than ALBI grade 1 patients (5-year CSS: 87.3% versus 92.8%; p=0.0247). In multivariate analysis, ALBI grade 2/3 was an independent predictor of CSS (HR=1.9; 95%CI=1.11-3.11; p=0.0177). ALBI grade was an independent prognostic factor in surgically resected NSCLC.

Normal Tissue Injury Induced by Photon and Proton Therapies: Gaps and Opportunities.

Despite technological advances in radiation therapy (RT) and cancer treatment, patients still experience adverse effects. Proton therapy (PT) has emerged as a valuable RT modality that can improve treatment outcomes. Normal tissue injury is an important determinant of the outcome; therefore, for this review, we analyzed 2 databases: (1) clinical trials registered with ClinicalTrials.gov and (2) the literature on PT in PubMed, which shows a steady increase in the number of publications. Most studies in PT registered with ClinicalTrials.gov with results available are nonrandomized early phase studies with a relatively small number of patients enrolled. From the larger database of nonrandomized trials, we listed adverse events in specific organs/sites among patients with cancer who are treated with photons and protons to identify critical issues. The present data demonstrate dosimetric advantages of PT with favorable toxicity profiles and form the basis for comparative randomized prospective trials. A comparative analysis of 3 recently completed randomized trials for normal tissue toxicities suggests that for early stage non-small cell lung cancer, no meaningful comparison could be made between stereotactic body RT and stereotactic body PT due to low accrual (NCT01511081). In addition, for locally advanced non-small cell lung cancer, a comparison of intensity modulated RTwith passive scattering PT (now largely replaced by spot-scanned intensity modulated PT), PT did not provide any benefit in normal tissue toxicity or locoregional failure over photon therapy. Finally, for locally advanced esophageal cancer, proton beam therapy provided a lower total toxicity burden but did not improve progression-free survival and quality of life (NCT01512589). The purpose of this review is to inform the limitations of current trials looking at protons and photons, considering that advances in technology, physics, and biology are a continuum, and to advocate for future trials geared toward accurate precision RT that need to be viewed as an iterative process in a defined path toward delivering optimal radiation treatment. A foundational understanding of the radiobiologic differences between protons and photons in tumor and normal tissue responses is fundamental to, and necessary for, determining the suitability of a given type of biologically optimized RT to a patient or cohort.

Decreased HLF Expression Predicts Poor Survival in Lung Adenocarcinoma.

BackgroundLung adenocarcinoma (LUAD) is a type of non-small cell carcinoma. Its pathogenesis is being explored and there is no cure for the disease.Material/MethodsThe Gene Expression Omnibus (GEO) was searched to obtain data on expression of messenger RNA. GEO2R, an interactive web tool, was used to calculate the differentially expressed genes (DEGs) in LUAD. All the DEGs from different datasets were imported into VENNY 2.1 (https://bioinfogp.cnb.csic.es/tools/venny/index.html) to identify the intersection of the DEGs. An online analysis tool, the Database for Annotation, Visualization, and Integrated Discovery (DAVID), was used to help understand the biological meaning of DEG enrichment in LUAD. Cytoscape 3.7.2 was used to perform centrality analysis and visualize hub genes and related networks. Furthermore, the prognostic value of the hub genes was evaluated with the Kaplan-Meier plotter survival analysis tool.ResultsThe GEO database was used to obtain RNA sequencing information for LUAD and normal tissue from the GSE118370, GSE136043, and GSE140797 datasets. A total of 376 DEGs were identified from GSE118370, 248 were identified from GSE136403, and 718 DEGs were identified from GSE140797. The 10 genes with the highest degrees of expression – the hub genes – were CAV1, TEK, SLIT2, RHOJ, DGSX, HLF, MEIS1, PTPRD, FOXF1, and ADRB2. In addition, Kaplan-Meier survival evaluation showed that CAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 were associated with favorable outcomes for LUAD.ConclusionsCAV1, TEK, SLIT2, HLF, MEIS1, PTPRD, FOXF1, and ADRB2 are hub genes in the DEG interaction network for LUAD and are involved in the development of and prognosis for the disease. The mechanisms underlying these genes should be the subject of further studies.

Open-label, phase II study of ladiratuzumab vedotin (LV) for castration-resistant prostate cancer (SGNLVA-005, trial-in-progress).

TPS185 Background: LIV-1 is a transmembrane protein expressed in a variety of cancer types. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death. In a phase 1 study, LV was tolerable and active in heavily pretreated patients with metastatic breast cancer (Modi 2017). This study is currently evaluating the safety and efficacy of LV in different advanced solid tumors with various LIV-1 expression, including metastatic castration-resistant prostate cancer (mCRPC), advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (squamous and nonsquamous), head and neck squamous cell carcinoma, and melanoma. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy in patients with previously treated, locally advanced unresectable or metastatic advanced solid tumors, including mCRPC. Patients with mCRPC will receive LV administered as a 30 minute intravenous infusion (IV) at 1.25 mg/kg every 1 week. Up to 30 patients with mCRPC will be enrolled. Patients in the mCRPC cohort must have metastatic castration-resistant disease, have received no more than 1 prior line of androgen receptor-targeted therapy, have ≥28 days between androgen receptor-targeted therapy and start of study treatment, an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, and adequate organ function. In addition, mCRPC patients with measurable and non-measurable disease are eligible if the protocol-defined criteria are met. mCRPC patients must not have BRCA gene mutations, prior cytotoxic chemotherapy in the metastatic mCRPC setting, prior radioisotope therapy, or radiotherapy to ≥30% of bone marrow. Patients are not preselected based on tumor LIV-1 expression. Their tumor samples will be analyzed for correlation between LIV-1 expression and response. Safety and efficacy will be monitored throughout the study. Study objectives include objective tumor response rate per RECIST 1.1 and prostate-specific antigen (PSA) response rate per Prostate Cancer Clinical Trials Working Group 3 (both primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study accrual is ongoing in the USA, Italy, South Korea, Taiwan, Australia, and the UK. Clinical trial information: NCT04032704.

The role for chemotherapy in 80 years and older patients with metastatic non-small cell lung cancer: A National cancer database analysis

BackgroundThere are limited data on the role for chemotherapy in patients > 80 years old with advanced stage non-small cell lung carcinoma (NSCLC). We used the National Cancer Database (NCDB) to evaluate treatment patterns and outcomes for patients ≥80 years old with advanced NSCLC. MethodsWe identified patients diagnosed with metastatic NSCLC between 2004 and 2014. We divided them into two groups: < 80 years old (n = 218,365) and ≥ 80 years old (n = 33,352). Patient characteristics including median age at diagnosis, gender, ethnicity, histology, chemotherapy status, tumor grade, treatment center, insurance status, income, education, and Charlson-Deyo co-morbidity index were collected. Continuous variables were compared using t-test and categorical variables were compared using chi-square or Fisher's exact test. Multivariable (MV) and propensity matched analyses were performed to analyze the impact of chemotherapy on overall survival. ResultsWe identified 33,352 patients > 80 years old diagnosed with advanced NSCLC. Only 29 % received chemotherapy, those who received chemotherapy had improved median overall survival of 8 months compared to 2 months in patients not receiving chemotherapy; adjusted hazards ratio (HR) 0.46; confidence interval (CI) 0.45−0.47; p < .001. MV analysis showed benefit of chemotherapy in all age subgroups (80–84 years, 85–89 years and 90+ years; p < .0001) and it was confirmed by propensity matched analysis. Patients receiving multiagent chemotherapy had improved 1-year survival of 35.5 % compared to 32.8 % with single agent chemotherapy (adjusted HR 0.92; CI 0.88−0.96; p < .001). Despite benefit from chemotherapy, the proportion of patients age ≥ 80 years receiving chemotherapy did not change over time. ConclusionsChemotherapy improved overall survival in ≥80 years old patients with advanced stage NSCLC. Despite improved survival and an increase in the proportion of ≥80 years old patients diagnosed with advanced NSCLC, less than one-third receive chemotherapy.

Clinical profile of cases of lung malignancy- A retrospective analysis by department of pulmonary medicine at tertiary care hospital, Sola, Ahmedabad

Background and Aim: Fibre optic video bronchoscopy (FOB) is a very safe and highly sensitive investigation for patients in whom we suspect lung malignancy. Bronchoscopy revolutionized early diagnosis of lung cancer by providing cytological and histological specimen in form of bronchoalveolar lavage and bronchial biopsy. In present study we describe our experience of performing bronchoscopy in patients of suspected lung malignancy. Methodology: Present study is retrospective observational study performed at tertiary care hospital, Sola, Ahmedabad over a period of one year. In this study 40 patients with suspected lung mass in CT underwent bronchoscopy after obtaining well informed written consent. A detailed clinical history, physical examination and necessary investigations were also done. Results: Of the 40 cases, 30 (75%) were male and 10 (25%) were female. The mean age in this study was 63 years. Squamous cell carcinoma was most common type present in 17.5% of participant, while second most common was adenocarcinoma. Small cell carcinoma was present in 4% and carcinoid was present in 5%. Undifferentiated non-small cell carcinoma was present in 20%. The yield of the study was 60%. Conclusions: Lung cancer is common malignancy. Bronchial biopsy has very high diagnostic yield. Bronchoscpoic techniques are safe and most precise tool for early diagnosis of suspected lung mass. Keywords: Biopsy, Bronchoalveolar lavage, Fibreoptic bronchoscopy, Lung cancer.

A prognosis-related molecular subtype for early-stage non-small lung cell carcinoma by multi-omics integration analysis

BackgroundEarly-stage non-small cell lung carcinoma (NSCLC) accounts for more than 80% of lung cancer, which is a kind of cancer with high heterogeneity, so the genetic heterogeneity and molecular subtype should be explored.MethodsPartitioning Around Medoid algorithm was used to acquire the molecular subtype for early-stage NSCLC based on prognosis-related mRNAs and methylation sites. Random forest (RF) and support vector machine (SVM) were used to build prediction models for subtypes.ResultsSix prognosis-related subtypes for early-stage NSCLC, including 4 subtypes for lung squamous cell carcinoma (LUSC) and 2 subtypes for lung adenocarcinoma (LUAD), were identified. There were highly expressed and hypermethylated gene regions for LUSC-C1 and LUAD-C2, highly expressed region for LUAD-C1, and hypermethylated regions for LUSC-C3 and LUSC-C4. Molecular subtypes for LUSC were mainly determined by DNA methylation (14 mRNAs and 362 methylation sites). Molecular subtypes for LUAD were determined by both mRNA and DNA methylation information (143 mRNAs and 458 methylation sites). Ten methylation sites were selected as biomarkers for prediction of LUSC-C1 and LUSC-C3, respectively. Nine genes and 1 methylation site were selected as biomarkers for LUAD subtype prediction. These subtypes can be predicted by the selected biomarkers with RF and SVM models.ConclusionsIn conclusion, we proposed a prognosis-related molecular subtype for early-stage NSCLC, which can provide important information for personalized therapy of patients.

Outcomes of Patients with Pulmonary Large Cell Neuroendocrine Carcinoma in I-IV Stage.

Background and Objectives: Large cell neuroendocrine cancer is characterised by poor prognosis. The standard of treatment is still not established. The aim of this study was to assess the predictive factors of overall survival (OS) and progression-free survival (PFS) of pulmonary large cell neuroendocrine carcinoma (LCNEC) and combined LCNEC. Materials and Methods: All patients had confirmed pathology stage I-IV disease recorded between period 2002–2018. Survival curves were estimated by Kaplan–Meier method. Uni- and multivariable analysis was conducted using Cox-regression analysis. Results: A total of 132 patients with LCNEC and combined LCNEC were included. Half of them had clinical stage IIIB/C-IV. Patients were treated with radical (n = 67, including surgery alone; resection with neo-adjuvant or adjuvant chemotherapy, radiochemotherapy, or adjuvant radiotherapy; patients treated with radiochemotherapy alone), palliative (n = 41) or symptomatic (n = 24) intention. Seventeen patients were treated with resection margin R1 or R2. Non-small cell carcinoma (NSCLC) chemotherapy (platinum-vinorelbine; PN schedule) and small-cell lung carcinoma (SCLC) chemotherapy approaches (platinum/carboplatinum-etoposide; PE/KE schedule) were administered in 20 and in 55 patients, respectively. The median (95% Confidence Interval (CI)) OS and PFS were 17 months (9.0–36.2 months) and 7 months (3.0–15.0 months), respectively. Patients treated with negative resection margin, with lower clinical stage, without lymph node metastasis, and with size of primary tumour ≤4 cm showed significantly better OS and PFS. The main risk factors with an adverse effect on survival were advanced CS and positive resection margin. Conclusions: Patients with LCNEC characterized poor prognosis. Independent prognostic factors influencing PFS were initial clinical stage and resection margin R0 vs. R1-2.

Acute kidney Injury due to Alectinib, an Anaplastic Lymphoma Kinase inhibitor

Introduction: The array of unintended effects of targeted oncological treatments is still being elucidated. Cognizance of these effects is important since they allow early identification and intervention. Methods: We report a case of progressive reduction in kidney function following the introduction of the oral second generation Anaplastic Lymphoma Kinase (ALK) Inhibitor: Alectinib for the treatment of metastatic non-small cell carcinoma of the lung (NSCLC). Kidney biopsy findings suggested that the predominant manifestation was acute tubular injury, which resolved with cessation of Alectinib therapy and did not recur with the introduction of the third generation ALK inhibitor Lorlatinib. Conclusions: This case report adds to the Onco-Nephrology literature in relation to the potential nephrotoxic effects of ALK inhibitors.

Treatment at Integrated Centers Might Bridge the Academic-Community Survival Gap in Patients With Metastatic Non-Small Cell Carcinoma of the Lung

BackgroundNon-small cell lung cancer (NSCLC) is responsible for the most cancer-related deaths in the United States. A better understanding of treatment-related disparities and ways to address them are important to improving survival for patients with metastatic NSCLC. Materials and MethodsWe performed a retrospective analysis using the National Cancer Database. Included in this analysis were 107,116 patients with metastatic NSCLC who were treated at academic centers (AC), community-based centers (CC), and integrated centers (IC) between 2004 and 2015. The primary end point was overall survival, with comparisons of AC, CC, and IC. ResultsThe survival disparity between AC and CC continued to grow over the study period, from a 5.7% difference in 2-year survival to a 7.5% difference. Treatment at IC was initially associated with survival similar to CC (hazard ratio [HR], 0.93), however, later in the study period treatment at IC improved (HR, 0.74) outpacing the improvement in survival in CC (HR, 0.82) but not to the same degree as the improvement in AC (HR, 0.64). The improvement in survival at IC was noted predominantly in patients with adenocarcinoma (HR, 0.72; P < .001) but not in squamous-cell carcinoma (HR, 0.89; P value not significant). ConclusionTreatment of metastatic NSCLC at IC was associated with improved survival during our study period compared with treatment at CC. This appeared to be histology-dependent, suggesting a treatment-related improvement in survival because over this period newer therapies were preferentially available for adenocarcinoma. Integrating care across treatment facilities might be one way to bridge the growing gap in survival between AC and CC.