Small Cell Carcinoma Of The Lung Research Articles

NEUROENDOCRINE TUMORS OF THE GENITOURINARY TRACT - A CLINICAL AND PATHOLOGIC REVIEW

Abstract Introduction/Objective Neuroendocrine tumors (NETs) of the genitourinary (GU) tract are rarely seen during daily surgical pathology sign-out sessions and comprise a heterogeneous group of neoplasms. We undertook a retrospective study to assess the clinical and pathologic characteristics of this unusual group of neoplasms involving the GU tract. Methods/Case Report We performed a retrospective review of the surgical pathology files for NETs of the GU tract between July 1993 and December 2021. Chart review was performed for the clinical and pathologic findings. Results (if a Case Study enter NA) A total of 26 patients were identified. There were 18 males and 8 females ranging in age from 43 to 94 years (mean age 69 years). 19/26 (73%) cases were primary tumors; 9 bladder small cell carcinoma, 5 prostatic small cell carcinoma, 4 bladder paragangliomas, and 1 case of small cell carcinoma of the renal pelvis. 7/26 (27%) cases were metastatic tumors; 5 Merkel carcinoma (3 urinary bladders, 2 testes), and 2 small cell carcinoma of the lung to the kidney. Conclusion The majority of NETs of the GU are primary and urinary bladder to be the most common site. Merkel cell carcinoma appears to have a tendency to metastasize to the GU tract, especially to the testis.

Clinical and Pathologic Differences between Small-Cell Carcinoma and Large-Cell Neuroendocrine Carcinoma of the Lung.

Both small-cell carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) of the lung are often clinically dealt with as being in the same category as neuroendocrine carcinoma, and their clinical differences have not been adequately assessed. The postoperative prognosis was retrospectively analyzed using the data of 196 patients who underwent resection for SCLC or LCNEC. Of the patients included, 99 (50.5%) had SCLC and 97 (49.5%) had LCNEC. The median duration of follow-up was 39 months (interquartile range [IQR] 21-76) and 56 months (IQR 21-87) for SCLC and LCNEC, respectively. The estimated 5-year overall survival (OS) probabilities were 53.7% and 62.7% (p = 0.133) for patients with SCLC and LCNEC, respectively. In the SCLC group, a multivariate analysis showed that adjuvant chemotherapy (hazard ratio 0.54, 95% confidence interval 0.30-0.99, p = 0.04) was the only factor that was significantly associated with OS. In the LCNEC group, univariate analyses demonstrated that pathologic stage I (p = 0.01) was the only factor that was associated with better OS after surgery. We found different clinical features in SCLC and LCNEC; in patients with SCLC, because OS could be expected to significantly improve with postoperative adjuvant chemotherapy, patients with resected SCLC of any pathologic stage should receive adjuvant chemotherapy. For patients with LCNEC, because pathologic stage I LCNEC is related to better prognosis than any other stages, a thorough clinical staging, including invasive staging, according to present guidelines should be performed to identify clinical stage I LCNEC with the highest certainty.

Small Cell Carcinoma of the Rectum-An Unexpected Diagnosis: Current Treatment Options for a Rare and Aggressive Entity.

Rectal small cell carcinoma is a rare and aggressive cancer subtype for which a consensus of optimal treatment has not yet been reached. This cancer presents a difficult surgical problem, and thus, the mainstay of treatment tends to mirror that of small cell carcinoma of the lung (chemotherapy, radiation therapy, and immune modulators). This brief report highlights current treatment options available for this rare and difficult entity. There is a significant need for large-center clinical trials and prospective studies to help determine the best treatment regimen to effectively care for patients with small cell carcinoma of the rectum.

Efficacy of first-line checkpoint inhibitors in combination with chemotherapy in high-grade extrapulmonary metastatic neuroendocrine carcinomas.

Poorly differentiated extrapulmonary neuroendocrine carcinomas (EP NECs) are aggressive cancers characterized by a high Ki-67 index, rapid tumor growth and poor survival, and are subdivided into small and large cell carcinoma. For small cell carcinoma of the lung, a pulmonary NEC, the combination of cytotoxic chemotherapy (CTX) and a checkpoint inhibitor (CPI) is considered standard therapy and superior to CTX alone. EP NECs are typically treated with platinum-based regimens, some clinicians have adopted the addition of a CPI to CTX based on data from trials in patients with small cell carcinoma of the lung. In this retrospective study of EP NECs, we report 38 patients treated with standard first-line CTX and 19 patients treated with CTX plus CPI. We did not observe any additional benefit of adding CPI to CTX in this cohort.

Recent Advances in the Management of Small Cell Carcinoma of the Uterine Cervix.

Small cell neuroendocrine carcinoma of the cervix (SCNEC) is a rare disease characterized by a higher incidence of lymphatic invasion, metastasis, and recurrence compared to the squamous cell carcinoma and adenocarcinoma subtypes. Furthermore, it is prone to early distant metastasis and has a poor prognosis. Chemotherapy has an important role in the management of cervical SCNEC. The effective treatment schemes for early-stage SCNEC are local treatment with radical surgery and systemic chemotherapy. However no standard treatment regimen exists because of a rare disease. We reviewed previous reports to determine whether etoposide/platinum, which is used for histopathologically similar small cell carcinoma of the lung, is an appropriate initial chemotherapy regimen for SCNEC of the cervix. In this review the Cochrane library sources, ClinicalTrials.gov, Web of Silence, PubMed and search engine of Google scholar were searched for all interventional studies, reviews, case reports and meta-analyses published in 1997-2021. Etoposide/platinum (EP) is the most commonly used regimen and paclitaxel/carboplatin is the second most common, used as a part of multimodality therapy for SCNEC of the cervix in most studies. Cisplatin/vincristine/bleomycin, cisplatin/irinotecan, cisplatin/ifosfamide/etoposide were also reported in concurrence with EP; however no clinical trials are dedicated to SCNEC. Etoposide and platinum tend to have a better prognosis compared to other regimens used for other subtypes of cervical cancer. For recurrent cervical SCNEC, treatment options for patients are very limited. The application of molecular testing for targeted mutations may suggest potential future therapies that may be useful in this disease.

Severe hyponatremia as presenting symptom of small cell lung carcinoma

Abstract A 62-year-old female patient was admitted to ICU in our clinic with symptomatic severe hyponatremia with complaints of fatigue, vertigo, paresthesia of upper extremities and three episodes of loss of consciousness in the past month. She had been hospitalized two weeks before in neurology clinic because of the same symptoms. CT of the brain, EEG, ophthalmology examinations were negative. She did not complain of hemoptysis, cough, weight loss, fever, chest pain or dyspnea. Nephrologist was consulted and renal origin of the hyponatremia was excluded, before admission. Initial laboratory tests were glucose:5,47 umol/L,sodium:109 mEq/L,potassium;4.5 mEq/L,urea 3,9 umol/l;creatinine:52,7 mol/l,calcium:1,22umol/L,TSH 5;Cortisol 819nmol/L;ACTH:16,34 pg/ml. Her medical history included hypertension, primary hypothyroidism and history of smoking. Upon laboratory findings of low serum osmolality, high urine osmolality, high urine sodium levels and clinical euvolemia, and in the absence of renal, pituitary disfunction, adrenal insufficiency, inappropriate ADH syndrome was diagnosed and initially was treated with 3% NaCl. Since this treatment had no effect, it was started with fluid restriction, per os sodium intake was increased and therapy with loop diuretic was initiated, which resulted in correction of the hyponatremia. For the etiology consideration of inappropriate ADH syndrome CT of the thorax was performed, which revealed a neo infiltrative process with atelectasis in the poster basal segment of the left lobe. Histopathological sampling from the biopsy of the mass revealed small cell carcinoma of the lung. Metastasis were not detected. Since basal morning cortisol level was above upper range, with inappropriate measurements of ACTH constantly above 15 pg/ml, additional tests for ectopic Cushing syndrome were done. Overnight 1mg dexamethasone suppression test showed absent suppression of the morning cortisol values of 656nmol/L and ACTH of 22,14 pg/ml and absent circadian rhythm of cortisol secretion, with high measurements of midnight serum cortisol of 652 nmol/L. Diagnosis of ectopic Cushing syndrome and SIADH as part of paraneoplastic syndrome in small cell lung carcinoma was made. It is to be noted that patient had no significant symptoms or signs of hypercortisolemia. We report here a case of small cell carcinoma of the lung whose first presentation was with symptomatic hyponatremia as a result of inappropriate ADH syndrome. The most common neoplasms associated with hyponatremia are various forms of lung cancer. Because of the aggressive nature of the disease, the most common manifestation of small cell carcinoma of the lung is a metastatic one. Therefore, identifying the disease in earlier stages is very important. Unfortunately, these patients have low rates of survival and face a very poor prognosis even with treatment. The presence and early identification of paraneoplastic syndromes can be beneficial in this context.

Endobronchial Small Cell Lung Cancer Masquerading as Carcinoid Tumour in a Young Female: A Case Report

Bronchial Carcinoid Tumours also known as BCTs, are remarkable neuroendocrine malignancies that can denature chemical compounds with biological activity. Bronchial carcinoid tumours are also known as BCTs. The phrase “bronchial adenomas” was once used to refer to BCTs; however, this nomenclature is no longer utilised because BCTs are neither glandular nor invariably benign. Instead, the term “Bronchial Cystic Tumours” is used to refer to BCTs in this context (BCTs). They are normally a neoplasm that expands slowly and displays a variety of behaviours, yet, they are also capable of expanding rapidly and being significantly more aggressive in general. Despite the fact that smoking is a significant risk factor for Small Cell Lung Cancer (SCLC), which is a more severe form of lung cancer than carcinoid. In addition, surgery is still the treatment of choice for carcinoid tumours, although chemoradiation and chemotherapy are the only options for patients with stage four SCLC. Here the authors discuss the case of 30 years old young female patient, who was erroneously diagnosed with endobronchial carcinoid turned out to be a SCLC. Because of the significant connection between smoking and SCLC, malignancies are not usually seen in young females. The relevant patient’s investigations were consistent with a small cell carcinoma of the lung. Immunohistochemistry for CD56 and synaptophysin turned out to be positive. The patient received six cycles of chemotherapy with an injection of Cisplatin and an injection of Etoposide three weekly. She was followed-up after three months and did have symptomatic relief.

ODP245 Syndrome of Diabetic Ketoalkalosis due to Severe Hypercortisolemia: A Case Series

Abstract Introduction Decompensated diabetes (DM) precoma/comas states are major causes of hospital morbidity and mortality. These commonly include diabetic ketoacidosis (DKA), diabetic hyperglycemic hyperosmolar syndrome (DHHS), diabetic hypoglycemia coma (DHC) and diabetic lactic acidosis (DLA). Another less common decompensated DM precoma/coma state to be aware of is Diabetic ketoalkalosis (DKAL). We present two cases of DKAL due to severe hypercortisolemia (HCS) from ectopic Cushing's syndrome (ECS). Clinical cases; Case 1 was a 61 yr old AA woman with suboptimally managed type 2 DM who had been admitted for DKA 2 months before. She had marked hyperglycemia (blood glucose >500mg/dl) on repeated measures (RMs) and chronic diarrhea with tachypnea and altered mental status (AMS). She had heavy tobacco abuse and work up revealed a right lung mass biopsy of which showed a malignant neuroendocrine tumor presumed to be malignant bronchial carcinoid. Her initial lab tests showed marked metabolic alkalosis with severe hypokalemia and elevated anion gap, ketonemia and ketonuria. Presentation was typical of DKAL and subsequent work up showed ECS with serum cortisol > 110 (n; 4.3-22.4ug/dl) on RMs and serum ACTH 377-480 (n; 0/46pg/ml). Her metabolic derangements were corrected and HCS managed with mild impact using ketaconazole and octreotide but she died within a month of admission with intractable septic shock despite parenteral antimicrobials. Case 2 was a 46 yr old Hispanic man with heavy tobacco abuse admitted on account of AMS, tachypnea and upper abdominal pain. He had severe hyperglycemia (blood glucose >750mg/dl on RMs) though not known to have DM. HBA1c was > 15% indicating undiagnosed DM. Initial lab tests showed marked respiratory and metabolic alkalosis, marked hyponatremia, hypokalemia, hypo-osmolality but with ketonemia and ketonuria. Presentation was consistent with DKAL. Work up showed a left lung lesion with pleural effusion shown to be small cell carcinoma of the lung. He was also found to have profound HCS (serum cortisol >150ug/d; on RMs) confirmed due to ECS with serum ACTH, 1500-1800pg/ml. Metabolic derangements were corrected and he was started on ketoconazole and etomidate to correct HCS with little response. Elective bilateral adrenalectomy was planned but patient abruptly discharged himself AMA. He was readmitted ∼ 3 weeks later with a massive pulmonary embolism and acute respiratory failure from which he never recovered. He died ∼ 2 months later. Discussion + Conclusions DKAL is an uncommon but important potential acute presentation of decompensated DM. Early recognition and management requires close attention to the acid-base and electrolyte derangements that often accompany it. Among the many possible causes of DKAL severe HCS is an important possibility to be consider. Rapid diagnosis and institution of aggressive therapy of HCS is crucial as it often has high morbidity and mortality potential. Presentation: No date and time listed

Survival analysis of small cell carcinomas of the genitourinary system

Due to low incidence, there are no large prospective studies or clinical trials for small cell carcinoma (SCC) of the genitourinary system (GU), and most data are extrapolated from SCC of the lung. Using the SEER database, we analyzed incidence trends, overall survival, and cancer-specific survival using the log-rank test. Analysis of variables was performed using the Cox proportional hazards regression model. The analysis showed that SCC of the bladder and prostate were the most common types of GU SCC, with 1836 and 606 cases, respectively. In 2018, the incidence of SCC of the bladder and prostate was twice that of 2010 (P < 0.001). The overall survival and cancer-specific survival of patients with SCC of the bladder were significantly longer than those of patients with SCC of the prostate (P < 0.0001). SCC bladder patients with advanced age, more extensive growth, lymph node involvement, no surgical intervention, and the presence of the metastasis had worse survival outcomes (P < 0.05). The Asian/Pacific Islander race provided some survival benefits for patients with SCC of the bladder (P < 0.05). For patients with SCC of the prostate, only advanced age was a risk factor for poor outcomes (P < 0.05).

Molecular mechanism of Pulmonary diseases caused by exposure to urban PM2.5 in Chengdu-Chongqing Economic Circle, China.

Chengdu-Chongqing Economic Circle (CD-CQ Economic Circle) is one of China's four major economic circles and five major urban agglomerations located in Southwest China's Sichuan Basin. The CD-CQ Economic Circle, with its strong economic development and dense population, suffers from severe PM2.5 pollution, which is known to cause chronic and acute respiratory ailments. This study examined the lung disease-related hub genes, functions, and pathways that are affected by PM2.5 in summer and winter in the two central megacities of Chengdu and Chongqing. PM2.5 frequently activates lung disease-associated hub genes, most notably the transcription factor TP53. TP53 interacts with the majority of lung disease-related genes and regulates important and commonly occurring biological functions and pathways, including gland development, aging, reactive oxygen species metabolic process, the response to oxygen levels, and fluid shear stress, among others. Thus, PM2.5 has been shown to target TP53 for regulating lung disease genes/functions/pathways, thereby influencing the occurrence and progression of lung illnesses. Notably, PM2.5 may be associated with small cell carcinoma of the lung due to the high number of lung disease genes, hub genes, critical functions, and pathways enriched in this kind of cancer. These findings shed fresh light on the molecular pathophysiology of PM2.5 pollution on the respiratory system in the CD-CQ Economic Circle and aid in the development of novel techniques for mitigating PM2.5 pollution-associated respiratory illness.

Pulmonary Neuroendocrine Cells and Small Cell Lung Carcinoma: Immunohistochemical Study Focusing on Mechanisms of Neuroendocrine Differentiation.

Neuroendocrine (NE) differentiation has been histochemically detected in normal and cancer tissues and cells. Immunohistochemical analyses have provided a more detailed understanding of NE biology and pathology. Pulmonary NE cells are a rare lung epithelial type, and small cell carcinoma of the lung (SCLC) is a high-grade NE tumor. Pulmonary NE and SCLC cells share common mechanisms for NE differentiation. Neural or NE cell lineage-specific transcription factors, such as achaete-scute homologue 1 (Ascl1) and insulinoma-associated protein 1 (INSM1), are crucial for the development of pulmonary NE cells, and NE differentiation is influenced by the balance between Ascl1 and the suppressive neural transcription factor, hairy-enhancer of split 1, a representative target molecule of the Notch signaling pathway.In this review, we discuss the importance of Ascl1 and INSM1 in identifying pulmonary NE and SCLC cells and introduce Ascl1-related molecules detected by comparative RNA-sequence analyses. The molecular classification of SCLC based on the expression of lineage-specific transcription or co-transcription factors, including ASCL1, NEUROD1, POU2F3, and YAP1, was recently proposed. We attempted to characterize these 4 SCLC subtypes using integrated immunohistochemical studies, which will provide insights into the molecular characteristics of these subtypes and clarify the inter- and intratumor heterogeneities of SCLC.

A case of combined small cell carcinoma of the lung with carcinosarcoma

A case of combined small cell carcinoma of the lung with carcinosarcoma

Platinum Doublet plus Atezolizumab as First-line Treatment in Metastatic Large Cell Neuroendocrine Carcinoma: A Single Institution Experience

Background Large Cell Neuroendocrine Carcinoma of the Lung (L-LCNEC) is a rare type of neuroendocrine lung cancer that is increasingly diagnosed. However, the optimal management regarding the advanced stage is unclear. The purpose of this article is to present and compare our experience when L-LCNEC is treated as Small Cell Lung Cancer (SCLC). Patients and Methods Overall, eight cases of L-LCNEC were included. We retrospectively reviewed medical files and reports by accessing the Institution's Data of patients diagnosed with L-LCNEC from April 2019 until December 2020 and evaluated their response to the combination of Platinum – Etoposide – Atezolizumab as first-line chemotherapy. Results The overall observed response rate (ORR) of 75%. The median PFS was 6.85 months. The median response duration was 5.5 months. Conclusions Comparing our findings with other retrospective and prospective studies, it seems that the systematic treatment of choice and management in L-LCNEC of the lung should be that of a small cell carcinoma of the lung.

AN UNEXPECTED PULMONARY BIOPSY FINDING: SIMULTANEOUS SMALL CELL AND NON-SMALL CELL LUNG CANCER

TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: There are rare instances in which patients are found to have small cell and non-small cell lung cancer simultaneously. combined small cell lung cancer (cSCLC) is a rare type of SCLC in which a tumor contains SCLC and another non-small cell component. (1). Mutiple primary lung cancer (MPLC) occurs when malignancies develop at anatomically separate sites in the lungs. (2) CASE PRESENTATION: A 71-year-old female with a 60-year history of cigarette smoking presented with two weeks of generalized weakness and fatigue. A computerized tomography (CT) scan of the chest (Figure 1) revealed a large subpleural thick-walled cavitary mass in the right lower lobe (RLL) measuring 10 cm in the largest dimension. Additionally, there was a peribronchovascular mass in the right upper lobe with right-sided hilar and mediastinal adenopathy. Given the patient's clinical history and radiographic findings malignancy was suspected. Bronchoscopy with TBNA of mediastinal lymph nodes and the cavitary RLL mass was performed. Immunohistochemistry of the RLL mass biopsy was consistent with moderately differentiated invasive SCC. However, immunohistochemistry of the subcarinal lymph nodes biopsies revealed a different cancer type, high-grade SCLC. Based on the biopsy results, the diagnosis could have been either cSCLC in which separate biopsy sites sampled tumor different components or MPLC. Following these findings, the patient elected for comfort care. DISCUSSION: The ACCP guidelines for the diagnosis and management of lung cancer recommend that lung cancer diagnosis be made by the least invasive method possible which is often bronchoscopy with TBNA or endobronchial ultrasound-guided needle aspiration when extensive mediastinal disease is present. (3) In this case presentation, isolated sampling of subcarinal lymph nodes would have led to an incorrect or incomplete diagnosis, as the peripheral tumor site biopsy found an additional cancer type. While it is important to minimize morbidity associated with tumor tissue collection, bronchoscopists are also tasked with obtaining adequate samples for molecular and histologic subtyping of tumors. cSCLC and MPLC present a unique challenge because limited tissue sampling can lead to under diagnosis of these cancers. As such, these cancers are likely under underdiagnosed (1,2). When possible, maximizing tissue acquisition from tumor sites and nodal stations can help prevent misdiagnosis of cSCLC and MPLC. In both MPLC and cSCLC, characterization of all malignant cell lines is needed for the effective management of patients. CONCLUSIONS: cSCLC and MPLC are both important, likely under-diagnosed cancers to consider when investigating pulmonary tumors. Bronchoscopists should balance the need to minimize morbidity with the need for obtaining adequate tissue from nodal stations and tumor sites to prevent misdiagnosis of cSCLC and MPLC. REFERENCE #1: Zhao X, McCutcheon JN, Kallakury B, et al. Combined Small Cell Carcinoma of the Lung: Is It a Single Entity? Journal of Thoracic Oncology. 2018;13(2):237-245. REFERENCE #2: Chen C, Huang X, Peng M, Liu W, Yu F, Wang X. Multiple primary lung cancer: a rising challenge. J Thorac Dis. 2019;11(Suppl 4):S523-S536. doi:10.21037/jtd.2019.01.56 REFERENCE #3: Rivera MP, Mehta AC, Wahidi MM. Establishing the Diagnosis of Lung Cancer. Chest. 2013;143(5):e142S-e165S. doi:10.1378/chest.12-2353 DISCLOSURES: No relevant relationships by Amad Chohan, source=Web Response No relevant relationships by Hannah Hameed, source=Web Response No relevant relationships by Anjan Kumar, source=Web Response No relevant relationships by mohammad Razaq, source=Web Response No relevant relationships by Mashal Tahirkheli, source=Web Response

Anti-Yo antibody mediated paraneoplastic cerebellar degeneration with breast carcinoma: Rare case report

Paraneoplastic cerebellar degeneration is a rare, severely debilitating neurodegenerative syndrome with antibodies targeting Purkinje cells of the cerebellum. It has been associated with fever than 1% of cancers, including small cell carcinoma of the lung, breast cancer, Hodgkin lymphoma and gynaecologic malignancies. Anti-Yo antibody frequently associated with this syndrome and associated with poor prognosis We are reporting a rare case report of anti-Yo antibody mediated cerebellar degeneration in patient with highly aggressive carcinoma of breast.

Genomic analyses of high-grade neuroendocrine gynecological malignancies reveal a unique mutational landscape and therapeutic vulnerabilities.

High‐grade neuroendocrine carcinoma of gynecologic origin (NEC‐GYN) is a highly aggressive cancer that often affects young women. The clinical management of NEC‐GYN is typically extrapolated from its counterpart, small cell carcinoma of the lung (SCLC), but, unfortunately, available therapies have limited benefit. In our NEC‐GYN cohort, median progression‐free survival (PFS) and overall survival (OS) were 1 and 12 months, respectively, indicating the highly lethal nature of this cancer. Our comprehensive genomic analyses unveiled that NEC‐GYN harbors a higher mutational burden with distinct mutational landscapes from SCLC. We identified 14 cancer driver genes, including the most frequently altered KMT2C (100%), KNL1 (100%), NCOR2 (100%), and CCDC6 (93%) genes. Transcriptomic analysis identified several novel gene fusions; astonishingly, the MALAT1 lincRNA gene was found in ˜ 20% of all fusion events in NEC‐GYN. Furthermore, NEC‐GYN exhibited a highly immunosuppressive state, intact RB1 expression, and was uniquely enriched with the YAP1 high molecular subtype. Our study identifies several potential therapeutic targets and suggests an urgent need to re‐evaluate the treatment options for NEC‐GYN.

Predicting ROR1/BCL2 combination targeted therapy of small cell carcinoma of the lung

Small cell lung cancer (SCLC) remains a deadly form of cancer, with a 5-year survival rate of less than 10 percent, necessitating novel therapies. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (FFPE) SCLC patient samples were utilized to determine the prevalence of ROR1 and BCL2 expression in SCLC. Eight SCLC-derived cell lines were used to determine the antitumor activity of a small molecule ROR1 inhibitor (KAN0441571C) alone and in combination with the BCL2 inhibitor venetoclax. The Chou-Talalay method was utilized to determine synergy with the drug combination. ROR1 and BCL2 protein expression was identified in 93% (52/56) and 86% (48/56) of SCLC patient samples, respectively. Similarly, ROR1 and BCL2 were shown by qRT-PCR to have elevated expression in 79% (22/28) and 100% (28/28) of SCLC patient samples, respectively. KAN0441571C displayed efficacy in 8 SCLC cell lines, with an IC50 of 500 nM or less. Synergy as defined by a combination index of <1 via the Chou-Talalay method between KAN0441571C and venetoclax was demonstrated in 8 SCLC cell lines. We have shown that ROR1 inhibition is synergistic with BCL2 inhibition in SCLC models and shows promise as a novel therapeutic target in SCLC.

P52.12 Incidence of Brain Metastasis in Advanced Non-Small Cell Lung Cancer at Presentation-An Experience From Tertiary Care Centre in South India

Brain metastasis is one of the most significant problems in patients with lung cancer. Many patients with brain metastasis are asymptomatic at presentation.Due to its prognostic significance and bad survival, many studies looked upon the incidence of brain metastasis at the presentation of NSCLC. Most of them are retrospective studies conductedin different parts of the world. To the best of our knowledge, the frequency of brain metastasis in patients with NSCLC at initial presentation in India has not been studied.So we planned a study to evaluate the incidence of brain metastasis in NSCLC patients treated in our center. It is a prospective observational study conducted in the department of medical oncology at our tertiary care center from Sep 2019- March 2020. A total of 80 patients with lung cancer were registered in the department. Among them,66 patients had advanced non- small cell carcinoma of the lung (NSCLC),and they were enrolled in the study.Clinical profile,performance status, demographic characteristics, smoking history, and imaging findings were noted at the time of presentation. MRI brain was taken for all advanced NSCLC patients,and the results were analyzed. . Mean age at presentation was 60 years. 20(30%) patients were smokers and 46(70%) were non-smokersAmong 66 patients, 33% had brain metastasis. 15 (63%) patients were adenocarcinoma, whereas 9 (27%) patients had squamous cell carcinoma. 42% had asymptomatic brain metastasis at presentation. All patients with brain metastasis received radiotherapy. Other parameters are tabulated as follows.Tabled 1Baseline CharacteristicsParametersNo of Patients (%)Mean Age60 yearsMale36 (54%)Female30 (46%)ECOG0-256 (85%)310 (15%)Brain Metastasis24 (33%)Male10 (42%)Female14 (58%)Adenocarcinoma15 (63%)Squamous Cell Carcinoma9 (37%)Asymptomatic14 (58%)Symptomatic10 (42%)Hemorrhagic5 (21%)Non-hemorrhagic19 (79%)Synchronous metastasis12 (18%)Contralateral Lung Metastasis6 (9%)Liver4 (6%)Bone2 (3%) Open table in a new tab Our study has found that incidence of brain metastasis is higher in South India when compared to western data. The other findings include female patients had slightly higher predilection for brain metastasis. Adenocarcinoma histology and synchronous contralateral lung metastasis are common in patients with brain metastasis. There are no validated biomarkers to predict brain metastasis in NSCLC due to its molecular heterogeneity. As the study was conducted in resources limited setting molecular correlation in patients with brain metastasis was not done. 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

P47.10 Predicting ROR1/BCL2 Combination Targeted Therapy of Small Cell Carcinoma of the Lung

P47.10 Predicting ROR1/BCL2 Combination Targeted Therapy of Small Cell Carcinoma of the Lung

Major Pathologic Response in Patients Treated for Non-small Cell Carcinoma of the Lung: Is There a Magic Number in the Histologic Sections to Be Evaluated?

Over the last years, great advancements have taken place in the medical approach to lung non-small cell carcinomas. Currently, with the use of biomarkers and diagnostic molecular pathology, tumors that in the past were treated with conventional chemotherapy, radiation therapy, or both, now similar patients afflicted by non-small cell carcinoma may have other alternative treatments. More importantly, because of those advancements in treatment options, it has become imperative that pathologists not only become familiar with the pathologic response to those treatments but also attempt to provide a pathologic assessment of the different changes that may be present as a result of a particular treatment. Even though for pathologists the demonstration of tumor necrosis and other inflammatory responses because of therapy as well as residual tumor does not represent a difficult task to accomplish, the issue is not in the diagnostic histopathologic assessment but in providing an adequate assessment of tumor viability as well as tumor necrosis and other histopathologic changes. More interesting is to acknowledge that it is in this particular area in which there may be differences in the approach because of the lack of a universal approach regarding how much of a particular tumor needs to be examined. Needless to say, the number of histologic sections examined may at the end be used as a specific parameter for tumor response to a particular treatment. The current review, will highlight, the different methodologies that over the years have been used or employed in the assessment of what is now referred as major pathologic response.