Clinical significance of brain metastases in patients with bronchopulmonary neuroendocrine tumors: A population-based analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21575-e21575
Author(s):  
Harry E Fuentes ◽  
Mojun Zhu ◽  
Jennifer Gile ◽  
Konstantinos Leventakos ◽  
Mohamad Bassam Sonbol ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Clinical Significance ◽  
Median Overall Survival ◽  
Stage Iv ◽  
Distant Metastases ◽  
Large Cell ◽  
Population Based ◽  
Histological Subtypes ◽  
Typical Carcinoid ◽  
Sizable Proportion

e21575 Background: The clinical significance of brain metastases in patients with bronchopulmonary neuroendocrine (NE) tumors is unknown; we therefore conducted a population based analysis to evaluate the implications of brain metastases in these patients. Methods: The NCDB database was queried to identify patients with stage IV bronchopulmonary NE tumors treated between the years of 2004-2012. Patients were split into two groups based on the presence of brain metastases at diagnosis and survival probabilities with multivariate models were performed. Results: A total of 7,725 patients with Stage IV bronchopulmonary NE tumors were identified. The histological subtypes studied in this cohort were NE carcinoma (65.4%), large cell NE carcinoma (30.5%), typical carcinoid (2.8%) and atypical carcinoid (1.3%) . The patients included in this study were mainly white (86.4%) men (56.8%) with a median age of 67 years who had liver (9.5%), bone (6.2%) and brain (5.9%) metastases at diagnosis. The median overall survival (OS) of the cohort was 5.59 (95% CI: 5.4-5.8) months, but when OS was stratified by histological subtype it was significantly better in patients with typical carcinoid (table). In the whole cohort, the median OS did not differ between patients with and without brain metastases (5.55 vs. 5.68; p = 0.24). However, a sensitivity analysis by histology showed that the presence of brain metastases worsen the median OS of patients with typical carcinoid only (15.1 vs 4.6, p = 0.04). An adjusted multivariate analysis restricted to patients with brain metastases showed that administration of systemic chemotherapy (HR:0.5; 95% CI:0.35-0.72, p < 0.001) and resection of distant metastases (HR:0.5; 95% CI:0.29-0.88, p = 0.017) were the two most powerful independent prognostic factors. Conclusions: The presence of brain metastases negatively impact survival of patients with typical carcinoids but not in those with the other histological subtypes included in this study. Staging MRI should be strongly considered at diagnosis in patients with bronchopulmonary NE tumors, due to the sizable proportion of these patients presenting with brain metastases and also due to its prognostic value in a subset of this population. [Table: see text]

DNA damage repair (DDR) pathway defects in gastrointestinal (GI) malignancies.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 647-647
Author(s):  
Ramya Thota ◽  
Gail Fulde ◽  
Mark Andrew Lewis ◽  
Derrick S. Haslem ◽  
Lincoln Nadauld ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Median Overall Survival ◽  
Parp Inhibitor ◽  
Stage Iv ◽  
Clinical History ◽  
Parp Inhibitors ◽  
Stage At Diagnosis ◽  
Damage Repair ◽  
Prostate Cancers ◽  
Generation Sequencing

647 Background: The clinical significance of the genomic alterations associated with DDR pathway in GI tumors (besides MMR defects) is largely unknown. These patients can potentially derive benefit from targeted therapy with poly ADP ribose polymerase (PARP) inhibitors, which have already shown promising activity in ovarian, breast and prostate cancers. In this study, we investigated the frequency and clinical significance of DDR repair defects (other than MMR defects) in GI tumors. Methods: We performed a retrospective analysis of all patients who had tumor next generation sequencing performed between January 2013 and August 2017 on GI cancers harboring DDR pathway defects. Data including demographics, clinical history, and treatment were extracted from patients' records. Results: Of 299 patients with GI tumors sequenced, 35 cases (12%) were noted to have DDR defects. The most commonly mutated genes – 6 (17%) BRCA2, 5 (14%) PALB2, 4 (11%) ATM, 3 (8.6%) BRCA1, 2 (5.7%) each of NBN, MUTYH, ERCC3, PARP1 amplification and 1 (2.8%) each of ERCC2, CDK12, and PARP2 amplification. Two patients had both ATM and BRCA2 mutations. Combination of ATM and MRE11, ATM and BRCA1, BRCA1 and ERCC6, BRCA2 and CDK12 were noted in 1 patient each. Of the 23 patients with available clinical data, the median age at diagnosis was 65 (range 30–85) years with male and female prevalence rates of 60.8% and 39.2%, respectively. Stage at diagnosis was I (n = 3), II (n = 3), III (n = 8), and IV (n = 9). The primary site of tumor was found in 8 (34.8%) colon, 4 (17.4%) liver, 4 (17.4%) pancreas, 2 (8.7%) esophagus, 2 (8.7%) anus, 2 (8.7%) appendix, 1 (4.3%) rectum. Seventeen patients received platinum‐based therapy, 7 were treated with PARP inhibitors and 5 patients received both platinum and PARP inhibitor. Median overall survival from diagnosis for patients with stage I/II was 65.3 months, stage III was 23.1 months, and stage IV was 22.4 months. The median survival of patients treated with olaparib was 24.5 months. Conclusions: DDR pathway defects in GI tumors are uncommon. However, they can potentially be targeted with PARP inhibitors with durable survival. Future clinical trials are warranted to explore the role to PARP inhibitors in these unique subset of patients.

scholarly journals Prognostic value of PD-L1 expression in bronchopulmonary neuroendocrine tumours

2021 ◽  
Author(s):  
Erik Rösner ◽  
Daniel Kaemmerer ◽  
Elisa Neubauer ◽  
Jörg Sänger ◽  
Amelie Lupp
Keyword(s):  
Somatostatin Receptor ◽  
Distant Metastases ◽  
Large Cell ◽  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Typical Carcinoid ◽  
Tumour Grading ◽  
Expression Levels ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded

Programmed death protein 1 (PD-1) and its ligand, PD-L1, have emerged as promising therapeutic targets for many types of cancer that overexpress PD-L1. However, data on PD-L1 expression levels in bronchopulmonary neuroendocrine neoplasms (BP-NEN) are limited and contradictory. In the present study, a total of 298 archived, formalin-fixed, paraffin-embedded BP-NEN samples from 97 patients diagnosed with typical carcinoid (TC), atypical carcinoid (AC), small cell lung cancer (SCLC), or large cell neuroendocrine carcinoma of the lung (LCNEC) were evaluated for PD-L1 expression by immunohistochemistry using the highly sensitive monoclonal anti-PD-L1 antibody 73-10. PD-L1 expression levels were semiquantitatively estimated by tumour grading. Of the 298 BP-NEN samples, 85% were positive for PD-L1 expression. PD-L1 immunostaining predominantly localized to the plasma membrane of both tumour cells and tumour-infiltrating immune cells. SCLC and LCNEC exhibited significantly higher PD-L1 expression levels than TC or AC. PD-L1 expression levels were also higher in patients with lymph node or distant metastases, in patients who smoked, and in patients who died during the follow-up period. Moreover, PD-L1 expression levels correlated positively with tumour grading, Ki-67 index and the expression of the chemokine receptor CXCR4 and negatively with the levels of somatostatin receptor 1 and chromogranin A. High tumour PD-L1 levels were associated with poor patient outcomes. In conclusion, PD-L1 expression is common in BP-NEN, increases with malignancy, and is associated with poor prognosis. Therefore, targeting the PD-1/PD-L1 axis could be a promising strategy for treating BP-NEN. PD-L1 may also represent a useful prognostic biomarker for this tumour entity.

Prognostic factors by histologic subtype in stage IV non-small cell lung cancer (NSCLC): A population-based survival analysis of data from the Surveillance, Epidemiology, and End Results (SEER) Program (1988–2003)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 11053-11053
Author(s):  
K. Cetin ◽  
D. S. Ettinger ◽  
Y. Hei ◽  
C. D. O'Malley
Keyword(s):  
Lung Cancer ◽  
American Indians ◽  
Stage Iv ◽  
Tumor Grade ◽  
Large Cell ◽  
Population Based ◽  
Tumor Characteristics ◽  
Histologic Subtype ◽  
Select Patient ◽  
Histologic Subtypes

11053 Background: Representing roughly 85% of all lung cancers, NSCLC is frequently diagnosed at an advanced stage and has a poor prognosis. To better understand the prognostic importance of select patient and tumor characteristics in late-stage disease, we examined survival in patients diagnosed with stage IV NSCLC. Methods: Data from SEER were used to study 53,319 patients with stage IV NSCLC diagnosed between 1988 and 2003, with follow-up through 2005. The distribution of cases according to time period of diagnosis and select patient and tumor characteristics was described for each histologic subtype (squamous; adenocarcinoma (bronchioloalveolar adenocarcinoma (BAC), non-BAC); large cell; and other/unknown). Kaplan-Meier and multivariate Cox proportional hazard models were used to examine the influence of these variables on overall survival by histologic subtype. Results: Most recent period of diagnosis (1998–2003 versus 1988–1992) conferred a survival advantage across histologic subtypes, independent of gender, age, ethnicity/race, tumor grade, and uptake of surgery/radiation. This was especially pronounced for those diagnosed with large cell tumors (adjusted hazard ratio (aHR): 0.76, 95% confidence interval (CI): 0.71–0.82). Similarly, females survived longer than males across histologic groups, particularly for those with BAC tumors (aHR: 0.77, 95% CI: 0.66–0.89). Increasing age was associated with reduced survival in all histologic subtypes except BAC, where prognosis was poorest in the youngest age group. The influence of ethnicity/race also varied with histology: compared to Whites, American Indians/Alaskan Natives with squamous tumors and Blacks with large cell tumors had a poorer prognosis, whereas Asians/Pacific Islanders with either non-BAC or large cell tumors demonstrated superior survival. Conclusions: Survival among stage IV NSCLC patients improved over the study period, which may reflect the use of third generation chemotherapy as well as better supportive care. Nonetheless, lung cancer remains a deadly disease, and the prognostic effect of demographic factors varies with histologic subtype. [Table: see text]

scholarly journals Incidence and Survival Outcomes in Patients with Lung Neuroendocrine Neoplasms in the United States

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1753
Author(s):  
Shrunjal Shah ◽  
Rohit Gosain ◽  
Adrienne Groman ◽  
Rahul Gosain ◽  
Arvind Dasari ◽  
...  
Keyword(s):  
Population Data ◽  
Large Cell ◽  
The United States ◽  
Population Based ◽  
Future Research ◽  
Neuroendocrine Neoplasms ◽  
Typical Carcinoid ◽  
Adjusted Incidence Rate ◽  
Future Research Directions ◽  
Adjusted Incidence

Background: The incidence and prevalence of neuroendocrine neoplasms (NENs) are rapidly rising. Epidemiologic trends have been reported for common NENs, but specific data for lung NENs are lacking. Methods: We conducted a retrospective analysis utilizing the Surveillance, Epidemiology, and End Results (SEER) database. Associated population data were utilized to report the annual age-adjusted incidence and overall survival (OS) trends. Trends for large-cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC) were reported from 2000–2015, while those for typical carcinoid (TC) and small cell lung cancer (SCLC) were reported from 1988–2015. Results: We examined a total of 124,969 lung NENs [103,890—SCLC; 3303—LCNEC; 8146—TC; 656—AC; 8974—Other]. The age-adjusted incidence rate revealed a decline in SCLC from 8.6 in 1988 to 5.3 in 2015 per 100,000; while other NENs showed an increase: TC increased from 0.57 in 1988 to 0.77 in 2015, AC increased from 0.17 in 2001 to 0.22 in 2015, and LCNEC increased from 0.16 in 2000 to 0.41 in 2015. The 5-year OS rate among SCLC, LCNEC, AC, and TC patients was 5%, 17%, 64%, and 84%, respectively. On multivariable analyses, OS and disease-specific survival (DSS) varied significantly by stage, sex, histological type, insurance type, marital status, and race, with a better survival noted in earlier stages, females, married, insured, Hispanic and other races, and urban population. Similarly, TC and AC had better survival compared to SCLC and LCNEC. Conclusion: The incidence of lung NENs is rising, possibly in part because of advanced radiological techniques. However, the incidence of SCLCs is waning, likely because of declining smoking habits. Such population-based studies are essential for resource allocation and to prioritize future research directions.

scholarly journals Outcome comparison of patients who develop leptomeningeal disease or distant brain recurrence after brain metastases resection cavity radiosurgery

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Achiraya Teyateeti ◽  
Paul D Brown ◽  
Anita Mahajan ◽  
Nadia N Laack ◽  
Bruce E Pollock
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Median Overall Survival ◽  
Recursive Partitioning ◽  
Leptomeningeal Disease ◽  
Resection Cavity ◽  
Whole Brain Radiation ◽  
Class 1 ◽  
Outcome Comparison ◽  
Brain Radiation

Abstract Background To compare the outcomes between patients with leptomeningeal disease (LMD) and distant brain recurrence (DBR) after stereotactic radiosurgery (SRS) brain metastases (BM) resection cavity. Methods Twenty-nine patients having single-fraction SRS after BM resection who developed either LMD (n = 11) or DBR (n = 18) as their initial and only site of intracranial progression were retrospectively reviewed. Results Patients developing LMD more commonly had a metachronous presentation (91% vs 50%, P = .04) and recursive partitioning class 1 status (45% vs 6%, P = .02). There was no difference in the median time from SRS to the development of LMD or DBR (5.0 vs 3.8 months, P = .68). The majority of patients with LMD (10/11, 91%) developed the nodular variant (nLMD). Treatment for LMD was repeat SRS (n = 4), whole-brain radiation therapy (WBRT; n = 5), resection + WBRT (n = 1), and no treatment (n = 1). Treatment for DBR was repeat SRS (n = 9), WBRT (n = 3), resection + resection cavity SRS (n = 1), and no treatment (n = 5). Median overall survival (OS) from time of resection cavity SRS was 15.7 months in the LMD group and 12.7 months in the DBR group (P = .60), respectively. Median OS in salvage SRS and salvage WBRT were 25.4 and 5.0 months in the nLMD group (P = .004) while 18.7 and 16.2 months in the DBR group (P = .30), respectively. Conclusions Following BM resection cavity SRS, nLMD recurrence is much more frequent than classical LMD. Salvage SRS may be considered for selected patients with nLMD, reserving salvage WBRT for patients with extensive intracranial disease without compromising survival. Further study with larger numbers of patients is needed.

scholarly journals RADT-09. TYPE AND TIMING OF SYSTEMIC THERAPY USE PREDICT SURVIVAL IN PATIENTS WITH BRAIN METASTASES TREATED WITH RADIATION THERAPY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii183-ii183
Author(s):  
Kevin Fan ◽  
Nafisha Lalani ◽  
Nathalie Levasseur ◽  
Andra Krauze ◽  
Lovedeep Gondara ◽  
...  
Keyword(s):  
Overall Survival ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Performance Status ◽  
Population Based ◽  
The Novel ◽  
Brain Radiotherapy ◽  
Prognostic Assessment ◽  
Baseline Variable ◽  
Extracranial Disease

Abstract PURPOSE We aimed to investigate whether systemic therapy (ST) use around the time of brain radiotherapy (RT) predicts overall survival for patients with brain metastases (BM). We also aimed to validate the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) in a population-based cohort. METHODS We used provincial RT and pharmacy databases to retrospectively review all adult patients in British Columbia, Canada, who received a first course of RT for BMs between 2012 and 2016. We used a randomly selected subset with complete baseline data to develop a multivariate analysis (MVA)-based nomogram including ST use to predict survival after RT and to validate the DS-GPA. RESULTS In our 3095-patient cohort, the median overall survival (OS) of the 999 recipients of ST after RT was 5.0 months (CI 4.1-6.0) longer than the OS of the 2096 non-recipients of ST after RT (p&lt; 0.0001): targeted therapy (HR 0.42, CI 0.37-0.48), hormone therapy (HR 0.45, CI 0.36-0.55) and cytotoxic chemotherapy (HR 0.71, CI 0.64-0.79). The OS of patients who discontinued ST after RT was 0.9 months (CI 0.3-1.4) shorter than the OS of those who did not receive ST before nor after RT (p&lt; 0.0001). A MVA in the 200-patient subset demonstrated that the traditional baseline variables: cancer diagnosis, age, performance status, presence of extracranial disease, and number of BMs predicted survival, as did the novel variables: ST use before RT and ST use after RT. The MVA-based nomogram had a bootstrap-corrected Harrell’s Concordance Index of 0.70. In the 179 patients within this subset with DS-GPA-compatible diagnoses, the DS-GPA overestimated OS by 6.3 months (CI 5.3- 9.8) (p= 0.0006). CONCLUSIONS The type and timing of ST use around RT predict survival for patients with BMs. A novel baseline variable “ST planned after RT” should be prospectively collected to validate these findings in other cohorts.

scholarly journals Leptomeningeal Carcinomatosis: A Clinical Dilemma in Neuroendocrine Neoplasms

Biology ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 277
Author(s):  
Leonidas Apostolidis ◽  
Jörg Schrader ◽  
Henning Jann ◽  
Anja Rinke ◽  
Sebastian Krug
Keyword(s):  
Brain Metastases ◽  
Median Overall Survival ◽  
Case Reports ◽  
Individual Case ◽  
Leptomeningeal Carcinomatosis ◽  
Neuroendocrine Neoplasms ◽  
Cns Involvement ◽  
Ki 67 ◽  
Sensory Deficits ◽  
Clinical Dilemma

Central nervous system (CNS) involvement by paraneoplastic syndromes, brain metastases, or leptomeningeal carcinomatosis (LC) in patients with neuroendocrine neoplasms (NEN) has only been described in individual case reports. We evaluated patients with LC in four neuroendocrine tumor (NET) centers (Halle/Saale, Hamburg, Heidelberg, and Marburg) and characterized them clinically. In the study, 17 patients with a LC were defined with respect to diagnosis, clinic, and therapy. The prognosis of a LC is very poor, with 10 months in median overall survival (mOS). This is reflected by an even worse course in neuroendocrine carcinoma (NEC) G3 Ki-67 >55%, with a mOS of 2 months. Motor and sensory deficits together with vigilance abnormalities were common symptoms. In most cases, targeted radiation or temozolomide therapy was used against the LC. LC appears to be similarly devastating to brain metastases in NEN patients. Therefore, the indication for CNS imaging should be discussed in certain cases.

scholarly journals A Review of the Significance in Measuring Preoperative and Postoperative Carcinoembryonic Antigen (CEA) Values in Patients with Medullary Thyroid Carcinoma (MTC)

Medicina ◽  
2021 ◽  
Vol 57 (6) ◽  
pp. 609
Author(s):  
Ioannis Passos ◽  
Elisavet Stefanidou ◽  
Soultana Meditskou-Eythymiadou ◽  
Maria Mironidou-Tzouveleki ◽  
Vasiliki Manaki ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Carcinoembryonic Antigen ◽  
Medullary Thyroid Carcinoma ◽  
Clinical Significance ◽  
Relevant Literature ◽  
Distant Metastases ◽  
Lymph Node Involvement ◽  
C Cells ◽  
Gastrointestinal Malignancies ◽  
Medullary Thyroid

Background and Objectives: Medullary thyroid carcinoma (MTC) accounts for 1–2% of all thyroid malignancies, and it originates from parafollicular “C” cells. Carcinoembryonic antigen (CEA) is a tumor marker, mainly for gastrointestinal malignancies. There are references in literature where elevated CEA levels may be the first finding in MTC. The aim of this study is to determine the importance of measuring preoperative and postoperative CEA values in patients with MTC and to define the clinical significance of the correlation between CEA and the origin of C cells. Materials and Methods: The existing and relevant literature was reviewed by searching for articles and specific keywords in the scientific databases of PubMedCentraland Google Scholar (till December 2020). Results: CEA has found its place, especially at the preoperative level, in the diagnostic approach of MTC. Preoperative CEA values >30 ng/mL indicate extra-thyroid disease, while CEA values >100 ng/mL are associated with lymph node involvement and distant metastases. The increase in CEA values preoperatively is associated with larger size of primary tumor, presence of lymph nodes, distant metastases and a poorer prognosis. The clinical significance of CEA values for the surgeon is the optimal planning of surgical treatment. In the recent literature, C cells seem to originate from the endoderm of the primitive anterior gut at the ultimobranchial bodies’ level. Conclusions: Although CEA is not a specific biomarker of the disease in MTC, itsmeasurement is useful in assessing the progression of the disease. The embryonic origin of C cells could explain the increased CEA values in MTC.

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