Metastatic Neuroendocrine Carcinoma Research Articles

Rare histological prostate cancer subtypes: Cancer-specific and other-cause mortality.

To assess cancer-specific mortality (CSM) and other-cause mortality (OCM) rates in patients with rare histological prostate cancer subtypes. Using the Surveillance, Epidemiology, and End Results database (2004-2020), we applied smoothed cumulative incidence plots and competing risks regression (CRR) models. Of 827,549 patients, 1510 (0.18%) harbored ductal, 952 (0.12%) neuroendocrine, 462 (0.06%) mucinous, and 95 (0.01%) signet ring cell carcinoma. In the localized stage, five-year CSM vs. OCM rates ranged from 2 vs. 10% in acinar and 3 vs. 8% in mucinous, to 55 vs. 19% in neuroendocrine carcinoma patients. In the locally advanced stage, five-year CSM vs. OCM rates ranged from 5 vs. 6% in acinar, to 14 vs. 16% in ductal, and to 71 vs. 15% in neuroendocrine carcinoma patients. In the metastatic stage, five-year CSM vs. OCM rates ranged from 49 vs. 15% in signet ring cell and 56 vs. 16% in mucinous, to 63 vs. 9% in ductal and 85 vs. 12% in neuroendocrine carcinoma. In multivariable CRR, localized neuroendocrine (HR 3.09), locally advanced neuroendocrine (HR 9.66), locally advanced ductal (HR 2.26), and finally metastatic neuroendocrine carcinoma patients (HR 3.57; all p < 0.001) exhibited higher CSM rates relative to acinar adenocarcinoma patients. Compared to acinar adenocarcinoma, patients with neuroendocrine carcinoma of all stages and locally advanced ductal carcinoma exhibit higher CSM rates. Conversely, CSM rates of mucinous and signet ring cell adenocarcinoma do not differ from those of acinar adenocarcinoma.

Rare histological prostate cancer subtypes: Cancer-specific and other-cause mortality.

To assess cancer-specific mortality (CSM) and other-cause mortality (OCM) rates in patients with rare histological prostate cancer subtypes. Using the Surveillance, Epidemiology, and End Results database (2004-2020), we applied smoothed cumulative incidence plots and competing risks regression (CRR) models. Of 827,549 patients, 1510 (0.18%) harbored ductal, 952 (0.12%) neuroendocrine, 462 (0.06%) mucinous, and 95 (0.01%) signet ring cell carcinoma. In the localized stage, five-year CSM vs. OCM rates ranged from 2 vs. 10% in acinar and 3 vs. 8% in mucinous, to 55 vs. 19% in neuroendocrine carcinoma patients. In the locally advanced stage, five-year CSM vs. OCM rates ranged from 5 vs. 6% in acinar, to 14 vs. 16% in ductal, and to 71 vs. 15% in neuroendocrine carcinoma patients. In the metastatic stage, five-year CSM vs. OCM rates ranged from 49 vs. 15% in signet ring cell and 56 vs. 16% in mucinous, to 63 vs. 9% in ductal and 85 vs. 12% in neuroendocrine carcinoma. In multivariable CRR, localized neuroendocrine (HR 3.09), locally advanced neuroendocrine (HR 9.66), locally advanced ductal (HR 2.26), and finally metastatic neuroendocrine carcinoma patients (HR 3.57; all p < 0.001) exhibited higher CSM rates relative to acinar adenocarcinoma patients. Compared to acinar adenocarcinoma, patients with neuroendocrine carcinoma of all stages and locally advanced ductal carcinoma exhibit higher CSM rates. Conversely, CSM rates of mucinous and signet ring cell adenocarcinoma do not differ from those of acinar adenocarcinoma.

Evaluating the significance of next-generation sequencing (NGS) testing in Indian patients with advanced malignancies: An observational study on clinical outcomes and treatment costs.

e15091 Background: The widespread use of Next-Generation Sequencing (NGS) panels to guide targeted therapy in advanced malignancies has raised questions regarding their real-world impact on clinical outcomes and affordability. Methods: This observational study included 126 patients, conducted between January 2022 and December 2023 aimed to assess the utility of NGS testing in both the initial and subsequent lines of treatment for Indian patients facing advanced malignancies. Results: In the first-line setting, NGS was extensively employed for patients with metastatic Colorectal Cancer (mCRC) and Non-Small Cell Lung Cancer (NSCLC). Analysis of RAS and BRAF mutations in mCRC patients (n=21) informed the choice between EGFR and VEGFR-directed therapy, resulting in a median Progression-Free Survival (PFS) of 7.5 months. In NSCLC patients (n=37), the NGS identified targetable mutations in 30 cases, leading to significantly improved mPFS (12 months vs 6 mo with chemotherapy alone). NGS was also employed for HRR, HRD and BRCA testing in advanced breast (n=45) and ovarian carcinoma (n=11), which helps in determining prognosis, role of targeted therapy and genetics. No adverse events noted till date. For patients undergoing subsequent lines of treatment (n=12), NGS detected targetable mutations in 9 cases. NGS revealed actionable mutations (ERBB2, CD74/NRG1fusion and KRAS12C mutation) in metastatic NSCLC patients (n=3), leading to appropriate treatment and PFS of 4-6 months. In metastatic NSCLC patients, T790M mutation was detected in 1 patient confering PFS of 6 months with change to Osimertinib and EGFR exon 20 insertion mutation detected in another, survival didn't improve with addition of amivantamab due to poor general condition. Alpelisib was started for PIK3CA mutation in metastatic Ca Breast (HR+,HEr2-), which was discontinued due to poor tolerance after 3 months. In Metastatic Neuroendocrine Carcinoma (NEC) Lung, detection of EGFR l858R mutation did not confer a PFS benefit despite the addition of Geftinib to chemotherapy. Due to financial constraints, targeted therapy couldn't be started for 2 patients with pathogenic target detected. Conclusions: The study's findings suggest that NGS testing offers tangible clinical benefits in both initial and subsequent lines of treatment for advanced malignancies in the Indian population. Despite the varying costs of NGS in India (ranging from 240 to 1800 USD), the data implies an overall affordability, making it a viable option for patients with advanced malignancies. However, NGS didn't improve outcomes in patients with rapidly progressing disease, poor general condition and financial constraints.

A case of metastatic HPV-related cervical small cell neuroendocrine carcinoma with varying cytomorphology found in cytological specimens of a solid organ transplant recipient.

Small cell neuroendocrine carcinoma (NEC) of the cervix is a rare gynecological malignancy, constituting 2%-5% of all such cases. As high-risk Human Papilloma Virus (HR-HPV) infections contribute to 85% of these tumors, small cell NEC poses a significant risk for solid organ transplant recipients, increasing their risk of progressive disease. We present a case of an uterine cervix small cell NEC with metastasis to the bladder and pleural cavities in a 53-year-old woman with a past medical history of kidney transplantation, who presented with abnormal uterine bleeding. The initial liquid preparation (ThinPrep) cytology stained with Papanicolaou (Pap) showed an adenocarcinoma not otherwise specified. At the time of diagnosis, the patient had diffusely metastatic disease. A subsequent uterine cervix biopsy was consistent with a small cell NEC. Despite treatment with chemotherapy, the patient's condition deteriorated, evidenced by a worsening right-sided pleural effusion one-month postdiagnosis. A pleural effusion showed a tumor with glandular features, with immunohistochemistry suggestive of metastatic adenocarcinoma. HR HPV E6/E7 RNA in situ hybridization (ISH) was positive. Bladder washing showed cytopathologic findings consistent with bladder involvement by small cell carcinoma. The patient's lesions in both urine and pleural fluids showed distinct cytomorphology. Within a year of diagnosis, the patient was declared deceased. This case highlights the existence of carcinoma admixed with NEC tumor, such as an HPV associated adenocarcinoma admixed with a NEC and underscores the elevated risk of HPV-related genital lesions in renal transplant patients. In patients with a history of solid organ transplant or other immunosuppressive conditions, there is an increased necessity for enhanced surveillance and appropriate cancer screening.

The Effectiveness of Atezolizumab in Metastatic Large Cell Neuroendocrine Carcinoma of the Lungs: Insights from the LANCE Pilot Study.

Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone. The primary outcomes measured were 12- and 24-month survival rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Of the 22 patients screened, 17 met the inclusion criteria and received either atezolizumab plus platinum-based chemotherapy (n = 10) or chemotherapy alone (n = 7). After a median follow-up of 23.3 months, the 12-month survival rate was 57.1% (95% CI: 32.6-100%) and 14.3% (95% CI: 2.33-87.7%) for the atezolizumab and the chemotherapy-only groups, respectively. The survival benefit for the atezolizumab group was sustained at 24 months (45.7% vs. 14.3%). Overall survival was significantly higher for the atezolizumab group, and PFS was non-significantly associated with the addition of atezolizumab (log-rank p = 0.04 and 0.05, respectively). This pilot study suggests that the addition of atezolizumab to standard platinum-based chemotherapy may provide a substantial survival benefit compared with chemotherapy alone in the first-line treatment of metastatic LCNEC.

Metastatic pulmonary neuroendocrine carcinoma associated with AVP deficiency and panhypopituitarism due to a hypothalamic metastasis

Metastatic pulmonary neuroendocrine carcinoma associated with AVP deficiency and panhypopituitarism due to a hypothalamic metastasis

Genetics-guided therapy in neuroendocrine carcinoma: response to BRAF- and MEK-inhibitors.

Metastatic neuroendocrine carcinoma (NEC) is associated with short survival. Other than platinum-based chemotherapy, there is no clear standard regimen. Current guidelines suggest that combination treatment with BRAF-inhibitors should be considered for patients with BRAF V600E-mutated NEC. However, since only eight such patients have been reported in the literature, our object was to confirm the validity of this recommendation. This was a single-center retrospective cohort study conducted at Uppsala University Hospital. The included patients 1) had a histopathologically confirmed diagnosis of NEC, 2) were diagnosed between January 1st, 2018 and December 31st, 2023, 3) had tumor tissue genetically screened by a broad next-generation sequencing (NGS) panel, and 4) showed a tumor mutation for which there is a currently available targeted therapy. We screened 48 patients diagnosed with NEC between January 1st, 2018 and December 31st, 2023. Twelve had been analyzed with a broad NGS-panel, and two had a targetable mutation. Both these patients harbored a BRAF V600E-mutated colon-NEC and were treated with BRAF- and MEK-inhibitors dabrafenib and trametinib in second-line. At first radiological evaluation (RECIST 1.1), both patients had a reduction of tumor size, which decreased by 31 and 40%. Both had short response periods, and their overall survival was 12 and 9 months. BRAF-mutated NEC is sensitive to treatment with BRAF- and MEK-inhibitor combination. These results further support that DNA sequencing should be considered as standard of care in NECs to screen for potential treatment targets.

Abstract CT090: DAREON™-7: A phase 1, open-label, dose escalation and expansion cohort trial of the delta-like ligand (DLL3)-targeting T-cell engager BI 764532, plus first-line platinum-based chemotherapy in patients with DLL3-positive (+) neuroendocrine carcinomas

Abstract Background Neuroendocrine carcinomas (NECs) have limited treatment options. DLL3 is highly expressed in NECs and is a promising treatment target. In an ongoing phase 1 trial (NCT04429087), BI 764532, a DLL3/CD3 IgG-like T-cell engager, was tolerable with clinical activity in patients with DLL3-positive (+) tumors, including those with small cell lung cancer and other NECs. Purpose DAREON™-7 (NCT06132113), a phase 1, open-label, dose-escalation (Part A) and dose-expansion (Part B) trial, aims to determine the maximum tolerated dose (MTD), recommended dose for expansion (RDE)/recommended phase 2 dose (RP2D), and the safety and efficacy of BI 764532 + platinum and etoposide in patients with DLL3+ NEC. Experimental design Part A: ~25 patients will receive intravenous BI 764532 (target dose after step-in dosing) plus carboplatin/etoposide (CE) until intolerable toxicity, or progression per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, or for a maximum of 36 months. BI 764532 dose escalation will be guided by a Bayesian logistic regression model with overdose control. Part B: 2 cohorts (~15 patients each) will receive BI 764532 at the RDE/RP2D + CE or cisplatin/etoposide (carboplatin/etoposide or cisplatin/etoposide are the most-used standard of care [SOC] regimens). Key inclusion criteria: patients must have no prior systemic treatment for DLL3+ locally advanced or metastatic NEC (extrapulmonary or unknown primary) or large cell NEC of the lung except for 1 cycle of standard platinum/etoposide regimen as first-line treatment prior to entering the treatment period of the trial; patients with localized NEC or resectable disease who received prior adjuvant therapy can participate in the trial if they experienced a treatment-free interval of &amp;gt;6 months prior to the diagnosis of metastatic disease; and patients must have at least 1 measurable lesion as defined per RECIST v1.1. Patients must be adequate candidates to receive platinum/etoposide as the SOC treatment. Primary endpoints: occurrence of dose-limiting toxicities (DLTs) in the MTD evaluation (Part A) and on-treatment (Part B) periods. Secondary endpoints: occurrence of DLTs and adverse events during the on-treatment period (Part B), and efficacy measured by objective response and duration of response (Part B). Enrollment is ongoing. Citation Format: Jaume Capdevila, Timon Vandamme, Patricia Niccoli, Saori Mishima, Ken Kato, Yiyuan Ma, Ping Sun, Lijiang Geng, Ulrich M. Lauer. DAREON™-7: A phase 1, open-label, dose escalation and expansion cohort trial of the delta-like ligand (DLL3)-targeting T-cell engager BI 764532, plus first-line platinum-based chemotherapy in patients with DLL3-positive (+) neuroendocrine carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT090.

Clinical efficacy of lurbinectedin in metastatic neuroendocrine carcinomas of the genitourinary tract: Multi-institutional real-world experience.

601 Background: Neuroendocrine carcinomas (NEC) of the genitourinary (GU) tract, including small cell (SC) NEC and large cell (LC) NEC, are rare aggressive malignancies. Although highly sensitive to cisplatin-based chemotherapy, GU metastatic NEC (mNEC) have limited data to support next therapies. Lurbinectedin, a marine-derived alkylating drug and a selective inhibitor of oncogenic transcription and DNA repair pathways, is FDA-approved for small cell lung cancer (SCLC) after progression on frontline platinum-based therapy, with a disease control rate (DCR) of 68.6%. It is unknown whether DCR is similar in SCLC and GU mNEC. Methods: We report the first multi-institutional series (n=14) of lurbinectedin in GU mNEC. Imaging-based best overall responses (BOR) were noted as complete (CR), partial (PR), stable (SD), progressive (PD) or non-evaluable (NE). DCR includes CR, PR, and SD. We use the Kaplan-Meier method for overall survival (OS) and progression-free survival (PFS) from lurbinectedin start date. We define duration of response (DoR) from response date to progression or last contact date for patients (pts) with CR or PR. Results: Most pts had a median age at metastasis of 70.5 years (ICR: 64-74.5) [Table]. Primary locations were bladder (7/14, 50%), prostate (5/14, 35.7%) and ureter (2/14, 12.3%). Histology at diagnosis mostly consisted of mixed or pure SCNEC, with one exception of LCNEC. Most pts had visceral disease, prior immunotherapy and at least 2 prior lines of therapy for mNEC before lurbinectedin (8/14, 57.1%). DCR was 6/14 (42.8%), including 5 bladder pts and 1 prostate pt. Among bladder pts, BOR included one CR (1/7, 14.3%) for the LCNEC case, 2 PR (2/7, 28.6%), 2 SD (2/7, 28.6%) and 2 PD (2/7, 28.6%). Most prostate and ureteral pts either progressed on lurbinectedin or were NE (Prostate: 1 PR, 2 PD, and 2 NE; Ureteral: 1 PD and 1 NE). For all 14 pts, median OS was 11.47 months (95% CI: 2.17-13.63) and median PFS was 2.8 mo (1.4-10.9). Median DoR was 7.38 mo (2.3-9.53) for 4 responding pts (CR or PR). Treatment was stopped due to progression (9/14, 64.3%), three adverse events [thrombocytopenia, electrolyte abnormalities, cerebrovascular accident] (3/14, 21.4%), and pt preference (1/14, 7.1%). Conclusions: Lurbinectedin offers encouraging responses (DCR: 5/7, 71.4%) close to those in SCLC, in previously treated bladder mNEC. One CR was noted for a bladder pt with LCNEC. Responses were less appreciated in prostate and ureteral mNEC due to NE responses and limited number. Larger cohorts are needed to confirm survival benefit and genetic analyses are warranted to identify characteristics of responders. [Table: see text]

2190P First-line atezolizumab in combination with platinum etoposide in patients with metastatic lung large cell neuroendocrine carcinoma (LCNEC)

2190P First-line atezolizumab in combination with platinum etoposide in patients with metastatic lung large cell neuroendocrine carcinoma (LCNEC)

Paclitaxel-carboplatin plus bevacizumab therapy for advanced neuroendocrine carcinoma of the uterine cervix: A retrospective case series.

There is no conclusive data on the prognosis of patients who receive paclitaxel-carboplatin (TC) plus bevacizumab therapy for advanced neuroendocrine carcinoma (NEC) of the uterine cervix, a rare histological subtype of cervical cancer. Thus, the aim of this study was to determine the efficacy of TC chemotherapy plus bevacizumab and bevacizumab single maintenance therapy for advanced NEC of the cervix. This was a retrospective review of patients who received TC plus bevacizumab therapy for metastatic, recurrent, or persistent NEC of the cervix at seven institutions between 2015 and 2020. Relevant data were extracted from the patients' medical records and analyzed. Seven patients, including six with small-cell NEC and one with large-cell NEC, were included for analysis. Three patients received bevacizumab single maintenance therapy following TC plus bevacizumab therapy, whereas four patients did not receive bevacizumab single maintenance therapy. The median overall survival and progression-free survival of the patients who received bevacizumab single maintenance therapy were longer than those of the patients who did not receive the therapy (34 months vs. 10.5 months and 19 months vs. 5 months, respectively). However, the patients who received bevacizumab single maintenance therapy had received cisplatin-based chemotherapy previously. On the premise that cisplatin-based chemotherapy is administered as the first-line treatment for advanced NEC of the cervix, bevacizumab single maintenance therapy following TC plus bevacizumab may be considered the second- or third-line treatment. However, the risk of adverse events, such as intestinal perforation, should be discussed with patients.

Surgical treatment of stage IV gastroenteropancreatic neuroendocrine carcinoma: Experience and outcomes in the United States.

Surgery for metastatic gastroenteropancreatic neuroendocrine carcinoma (GEP-NEC) has not been well-studied. This retrospective cohort study describes patients in the United States with stage IV GEP-NEC and their survival outcomes segregated by surgery. Patients diagnosed with stage IV GEP-NEC from 2004 to 2017 in the National Cancer Database were categorized into three groups: no surgery, primary site or metastatic site ("single-site") surgery, and primary site and metastatic site ("multisite") surgery. Factors associated with surgical treatment were identified, and risk-adjusted overall survival of each group was compared. Of 4171 patients included, 958 (23.0%) underwent single-site surgery and 374 (9.0%) underwent multisite surgery. The strongest predictor of surgery was primary tumor type. Compared with no surgery, the risk-adjusted mortality reduction associated with single-site surgery ranged from 63% for small bowel (HR = 0.37, 0.23-0.58, p < 0.001) NEC to 30% for colon and appendix NEC (HR = 0.70, 0.61-0.80, p < 0.001), while the mortality reduction associated with multisite surgery ranged from 77% for pancreas NEC (HR = 0.23, 0.17-0.33, p < 0.001) to 48% for colon and appendix NEC (HR = 0.52, 0.44-0.63, p < 0.001). We observed an association between extent of surgical intervention and overall survival for patients with stage IV GEP-NEC. Surgical resection should be further investigated as a treatment option for highly-selected patients with this aggressive disease.

Chemotherapy for the initial treatment of metastatic prostate adenocarcinoma and neuroendocrine carcinoma at diagnosis: real world application and impact in the SEER database (2004 -2018).

Randomized controlled phase III trials have reported significant improvements in disease response and survival with the addition of chemotherapy to androgen deprivation therapy for men presenting with metastatic prostate cancer. We examined the implementation of such knowledge and its impact within the Surveillance, Epidemiology, and End Results (SEER) database. The administration of chemotherapy for men with an initial presentation of metastatic prostate cancer from 2004 to 2018 in the SEER database and its association with survival outcomes was examined. Kaplan-Meier estimates were applied to compare survival curves. Cox proportion hazard survival models were used to analyze the association of chemotherapy and other variables with both cancer- specific and overall survival. A total of 727,804 patients were identified with 99.9% presenting with adenocarcinoma and 0.1% with neuroendocrine histopathology. Chemotherapy as initial treatment for men with de novo distant metastatic adenocarcinoma increased from 5.8% during 2004-2013 to 21.4% during 2014-2018. Chemotherapy was associated with a poorer prognosis during 2004-2013 but was associated with improved cancer-specific (hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.78-0.93, p=0.0004) and overall survival (HR= 0.78, 95% CI: 0.71-0.85, p < 0.0001) during 2014-2018. The improved prognosis during 2014-2018 was observed in patients with visceral or bone metastasis and most impactful for patients aged 71-80 years. These findings were confirmed by subsequent propensity score matching analyses. Furthermore, chemotherapy was consistently provided to 54% of patients with neuroendocrine carcinoma at diagnosis from 2004 to 2018. Treatment was associated with improved cancer-specific survival (HR= 0.62, 95% CI: 0.45-0.87, p=0.0055) and overall survival (HR= 0.69, 95% CI: 0.51-0. 94, p=0.0176) during 2014-2018 but not significant in earlier years. Chemotherapy at initial diagnosis was increasingly employed in men with metastatic adenocarcinoma after 2014 and consistent with the evolution of National Comprehensive Cancer Network (NCCN) guidelines. Benefits for chemotherapy are suggested after 2014 in the treatment of men with metastatic adenocarcinoma. The use of chemotherapy for neuroendocrine carcinoma at diagnosis has remained stable, and outcomes have improved in more recent years. Further development and optimization of chemotherapy continues to evolve for men with de novo diagnosis of metastatic prostate cancer.

Clinicopathologic Spectrum of Lysozyme-Associated Nephropathy

Lysozyme-associated nephropathy (LyN), a rare cause of kidney injury in patients with chronic myelomonocytic leukemia (CMML), has not been well described to date. We report the clinicopathologic spectrum of LyN from a multi-institutional series. We identified 37 native kidney biopsies with LyN and retrospectively obtained clinicopathologic data. Thirty-seven patients had a median age of 74 years and included 78% males. Their most common presentation was acute kidney injury (AKI) or AKI on chronic kidney disease (CKD) (66%) with median estimated glomerular filtration rate (eGFR) of 21.7 ml/min per 1.73 m2, and proteinuria of 1.7 g. A minority (15%) had partial Fanconi syndrome. Serum lysozyme levels were elevated in all tested. Hematologic disorder (n= 28, 76%) was the most common etiology, including CMML (n= 15), acute myeloid leukemia (n= 5), and myelodysplastic syndrome (MDS) (n= 5). Nonhematologic causes (n= 5, 14%), included metastatic neuroendocrine carcinoma (n= 3), sarcoidosis, and leprosy. Etiology was unknown in 4 (11%). Pathology showed proximal tubulopathy with abundant hypereosinophilic intracytoplasmic inclusions, with characteristic staining pattern by lysozyme immunostain. Mortality was high (8/30). However, among the 22 alive, including 85% treated, 7 had improved kidney function, including 1 who discontinued dialysis and 6 with increase in eGFR >15 ml/min per 1.73 m2 compared with eGFR at the time of biopsy. Increased awareness of the full clinicopathologic spectrum of LyN may lead to prompt diagnosis, earlier treatment, and potentially improved outcome of this rare entity.

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.

Abstract 3383: Liquid biopsy for PDL-1 status by analysis of cfRNA: Clinical data from a large community practice

Abstract PD-L1 testing via immunochemistry has become a widely used tool to predict response to immune checkpoint inhibitor (ICI) therapy in many tumor types. However this marker can be expressed heterogeneously, and can vary with time, treatment effects, and local factors including cytokine expression. Gene expression profiles of immunologically active genes are currently being studied to more accurately predict response to ICI treatment. To evaluate a potentially more straightforward way to accomplish this, we utilized an assay of cfRNA in plasma for PD-L1, utilizing a real-time PCR based assay (Circulogene, Inc, Birmingham, AL). The demonstrated limit of detection for PD-L1 RNA was 1 copy/ul. Results were reported as either not detected, or low at over 1%, or high at over 50%. We used the PCR 30th percentile Ct value corresponding to a tissue IHC PD-L1 of&amp;gt;50%, and the 66th percentile Ct value corresponding to a tissue PD-L1 expression of &amp;gt;1%. We then collected data on over 400 patients over a two year period at a large community oncology practice and at a university clinic (Florida Cancer Specialists and Atrium Health/Wake Forest-Baptist Comprehensive Cancer Center) who had a clinical necessity for molecular testing in a commercially available setting with a CLIA certified lab. In some cases the corresponding tissue PD-L1 testing was also available, and may have been either positive or negative.To date 41 patients have been found to have high levels of cfRNA for PD-L1. Their clinical course has been analyzed using the electronic medical record. Some patients have received standard of care therapy, and some have been given CPI therapy with or without chemotherapy, if the attending oncologist felt this to be the best palliative option. These include tumors such as CRPC, metastatic low grade neuroendocrine carcinoma and HR+ metastatic breast carcinoma, that have rarely been treated successfully with CPI therapy. Tumor types - all are stage IV solid tumor patients: 19 NSCLC, 7 breast carcinoma, 3 colorectal cancer, 3 castrate resistant prostate carcinoma, 9 other tumor types.Data collection for tumor response or clinical benefit on the 41 patients is ongoing and will be presented at the meeting, and compared to published CPI response data using standard tissue IHC testing. Citation Format: Lowell L. Hart, Magali Van den Bergh. Liquid biopsy for PDL-1 status by analysis of cfRNA: Clinical data from a large community practice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3383.

Multi-center, retrospective study of first-line systemic therapy ± immune checkpoint inhibition for metastatic neuroendocrine carcinoma of the urinary tract.

467 Background: Neuroendocrine, small cell, or large cell carcinoma originating from the urothelium (uro-NE/SCC/LCC) is rare. Outcomes for metastatic disease are dismal. Treatment is extrapolated from small cell lung cancer, for which immune checkpoint inhibitors (ICIs) have modest activity. Preliminary activity has been reported with ICI for uro-NE. We aimed to compare real-world progression-free survival (PFS) and overall survival (OS) between ICI-containing and non-ICI-containing regimens in the first line (1L) metastatic setting for uro-NE/SCC/LCC. Methods: We performed a retrospective study at 11 cancer centers. Patients (pts) who received systemic therapy (2011-2021) for biopsy confirmed metastatic uro-NE/SCC/LCC were included. Pts with metastasis within 6 months of (neo)adjuvant chemotherapy (CT) (n=16) were excluded from 1L analyses. Results: 102 pts with metastatic uro-NE/SCC/LCC were evaluable. 17 (16.7%) had NE histology, 81 (79.4%) SCC, and 4 (3.9%) LCC. NE/SCC/LCC was mixed with urothelial histology in 19 (18.6%). Primary tumors were most often in the bladder (84.3%, n=86), less frequently upper tract (11.8%, n=12) or urethra (3.9%, n=4). 42 pts (41.2%) were previously treated for localized disease, the rest were de novo metastatic (n=60, 58.8%). Pts who received an ICI in any line (n=61) had significantly longer OS (p=0.038) than pts that never received an ICI (n=41). As shown in the table, in the 1L, ICI-containing regimens (n=33) resulted in significantly longer PFS, but not OS or ORR compared to non-ICI regimens (n=53). Subdividing 1L regimens into ICI without CT (n=14), CT without ICI (n=53), or ICI + CT (n=19), both PFS and OS were significantly different with similar ORR. ICI w/o CT had the longest median PFS and OS with an ORR 57.1% comparable to CT regimens. Of 61 pts that received ICI in any line, 14 (23.0%) had an immune-related adverse event of any grade; 11 (18.0%) received steroids. Conclusions: This is the largest ever report of ICI for metastatic uro-NE/SCC/LCC. ICIs were associated with improved outcomes with expected added toxicity. Further prospective investigation of ICI regimens is warranted. [Table: see text]

Cover Image

CytopathologyVolume 34, Issue 2 p. i-i COVER IMAGEFree Access Cover Image First published: 05 February 2023 https://doi.org/10.1111/cyt.13216AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract Cover illustration: The cover image is based on the Case Report Cytokeratin and CD56 aberrant co-expression in diffuse large B-cell lymphoma, NOS misinterpreted as metastatic neuroendocrine carcinoma by FNAC by Veronika Kloboves Prevodnik et al., https://doi.org/10.1111/cyt.13190. Volume34, Issue2March 2023Pages i-i RelatedInformation

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Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

P373 An Unusual Occurrence of Right-sided Colonic Neuroendocrine Carcinoma in Ulcerative Colitis – A case report

Abstract Background It's estimated that inflammatory bowel disease (IBD) accounts for 1-2% of all colorectal cancer (CRC) cases. However, the mere presence of IBD increases the risk by 2 folds compared with the general population. It's been established that the most prevalent epithelial colonic malignancy linked to IBD is adenocarcinoma. Neuroendocrine neoplasms arising in the large intestines are extremely rare (rate &amp;lt;1%), even less common in association with IBD.(1) Herein, we report a 49 years-old male with a longstanding history of ulcerative pancolitis, who was found to have a metastatic right-sided colorectal neuroendocrine carcinoma (NEC). Methods Case Presentation A 49-years-old male patient, with a 13-years history of ulcerative pancolitis underwent a colonoscopy. It revealed a large ulcerated mass extending from the ileocecal valve into the proximal ascending colon highly suspicious for malignancy. Biopsy showed a large cell poorly differentiated NEC in the ascending colon. Tumor cells were positive for Synaptophysin and cytokeratin AE1/3, and a high Ki67. Serum Chromogranin A (CgA) and urine 5-hydroxyindoleacetic acid were high. Imaging was evident for a short segment circumferential wall thickening at the ascending colon and hepatic metastasis. The patient was planned to receive chemotherapy, but died before treatment. Results Discussion Risk of CRC increments linearly approximately 7 years following diagnosis of IBD. After 30 years of colitis, the incidence is estimated to be around 18%. NECs in particular are not frequently encountered in association with IBD, much less right-sided.(1) Colonic NECs are usually aggressive with a Ki67 typically greater than 20%, often present with metastasis with absence of a characteristic hormonal secretion picture.(2, 3) The incidence of NECs in association with Ulcerative Colitis (UC) is twice more frequent in males, with a mean age of 49.36, and development after a median of 15 years of UC first diagnosis. Majority of NECs were found in the left side of the colon, in the contrary to our patient. Prognosis was dismal in most cases, as most demonstrated a higher malignant potential compared to adenocarcinomas.(3) Early diagnosis of gastrointestinal NECs poses a challenge since it lacks a specific clinical presentation. Serum CgA level correlates with the tumor burden and overall survival. Additionally, studies demonstrating the role of endoscopic surveillance in colonic NECs early detection is scarce.(1,4) Conclusion Thorough understanding of the condition and its risk factors is crucial for a timely diagnosis, which maximizes the likelihood of a favorable prognosis. By reporting this case, we emphasize the importance of considering NEC as a differential diagnosis of CRC in IBD, particularly in UC patients.