Histopathological Subtypes and PD-L1 Expression in Primary Urethral Adenocarcinoma: A Series of 5 Cases

2021 ◽  
pp. 106689692098834
Author(s):  
Carlos Padilla-Ansala ◽  
Eugenia García-Fernández ◽  
Pilar González-Peramato
Keyword(s):  
Poor Prognosis ◽  
Clear Cell ◽  
Radical Surgery ◽  
Treatment Options ◽  
Death Receptor ◽  
Histological Subtypes ◽  
Inflammatory Infiltration ◽  
Programmed Death ◽  
Death Receptor Ligand ◽  
Limited Choice

Background and Objectives Urethral adenocarcinoma is a rare disease with poor prognosis that can display multiple histologic patterns and has an unclear histogenesis. Radical surgery with extensive periurethral resection is the preferred therapeutic approach. Both chemotherapy and radiotherapy have been used as complementary treatment options. Due to the tendency of these tumors to recur, treatment-associated complications, and the limited choice of therapeutic options, patient management can be difficult. Given the lack of literature regarding immunotherapy in urethral adenocarcinoma, our objective was to explore the expression of programmed death receptor-ligand 1 (PD-L1) throughout the different histological subtypes of primary urethral adenocarcinoma. Methods We reviewed all primary urethral adenocarcinomas diagnosed at our hospital between 1965 and 2019, performed immunohistochemical assays on the tissue blocks, classified them according to their histology and origin, and performed PD-L1 (22C3) immunohistochemistry assays in all cases. Results We found a total of 5 cases of primary urethral adenocarcinoma. All of the patients were women. One of the cases was a cribriform adenocarcinoma, 2 were columnar-mucinous adenocarcinomas, and 2 were clear cell adenocarcinomas. One of the clear cell adenocarcinomas strongly expressed PD-L1. In addition, a profuse inflammatory infiltration constituted by CD3-positive and CD8-positive T lymphocytes within tumor cells was observed in this case. None of the other cases showed PD-L1 expression. Conclusions In conclusion, some urethral adenocarcinomas may strongly express PD-L1 and thus could potentially allow the use of immunotherapy in selected cases of advanced or recurrent adenocarcinoma.

scholarly journals Programmed Death Receptor-1/Programmed Death Receptor Ligand-1 Blockade after Transient Lymphodepletion To Treat Myeloma

2013 ◽  
Vol 190 (11) ◽  
pp. 5620-5628 ◽  
Author(s):  
Tyce J. Kearl ◽  
Weiqing Jing ◽  
Jill A. Gershan ◽  
Bryon D. Johnson
Keyword(s):  
Death Receptor ◽  
Receptor Ligand ◽  
Programmed Death ◽  
Death Receptor Ligand

scholarly journals Targeting the PD-1/PD-L1 Pathway in Renal Cell Carcinoma

2019 ◽  
Vol 20 (7) ◽  
pp. 1692 ◽  
Author(s):  
Solène-Florence Kammerer-Jacquet ◽  
Antoine Deleuze ◽  
Judikaël Saout ◽  
Romain Mathieu ◽  
Brigitte Laguerre ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Programmed Death ◽  
Pathologic Features ◽  
Death Receptor Ligand ◽  
Antiangiogenic Drugs

Renal cell carcinoma encompass distinct diseases with different pathologic features and distinct molecular pathways. Immune checkpoint inhibitors targeting the programmed death receptor ligand 1 (PD-L1) / programmed death receptor 1 (PD-1) pathway alone or in combination have greatly changed clinical management of metastatic renal cell carcinoma, now competing with antiangiogenic drugs in monotherapy for first-line treatment. However, long-term response rates are low, and biomarkers are needed to predict treatment response. Quantification of PD-L1 expression by immunohistochemistry was developed as a promising biomarker in clinical trials, but with many limitations (different antibodies, tumour heterogeneity, specimens, and different thresholds of positivity). Other biomarkers, including tumour mutational burden and molecular signatures, are also developed and discussed in this review.

scholarly journals PD-L1 Status in Gastric Cancers, Association with the Transcriptional, Growth Factors, AKT/mTOR Components Change, and Autophagy Initiation

2021 ◽  
Vol 22 (20) ◽  
pp. 11176
Author(s):  
Liudmila Spirina ◽  
Alexandra Avgustinovich ◽  
Sergei Afanas’ev ◽  
Maxim Volkov ◽  
Alexey Dobrodeev ◽  
...  
Keyword(s):  
Molecular Markers ◽  
Cancer Progression ◽  
Combined Treatment ◽  
Death Receptor ◽  
Autophagic Flux ◽  
Gastric Cancers ◽  
Autophagy Induction ◽  
Programmed Death ◽  
Death Receptor Ligand ◽  
Main Regulator

Introduction: The programmed death receptor ligand 1 (PD-L1) immunohistochemistry (IHC) assay is a widely used selection method for pembrolizumab treatment in gastric cancer (GC) patients. PD-L1 is the main regulator of immunity in oncogenesis. Material and methods: The study included 38 patients with GC. The combined treatment consisted of neoadjuvant FOLFOX6, or FLOT, chemotherapy and surgery. PD-L1 + tumor status was recorded in 12 patients (CPS > 5), with a negative status recorded in 26 patients. RT-PCR determined the expression of molecular markers. The level of LC3B protein was detected by Western Blotting analysis. Results: An overexpression of PD-1, PD-L2 in the tumor is associated with AKT/mTOR mRNA profile change and autophagy initiation in IHC PD-L1 positive GCs. NACT influences these biological features, modifying the expression of AKT/mTOR components and autophagic flux. In PD-L1 positive cancers, the effect of NACT and molecular markers rearrangements are essential compared to the PD-L1 negative cancers. Conclusion: The IHC PD-L1 status in gastric cancers is the significant marker of cancer progression, recovering the multiple inner mechanisms of cancer spreading and leading to ineffective therapy. Autophagy induction and angiogenesis are found in PD-L1 positive gastric cancers.

scholarly journals Outcome of patients with advanced endometrial and cervical cancer treated in a phase 1 unit.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5597-5597
Author(s):  
Rowan Miller ◽  
Michael-John Devlin ◽  
Nicholas Fraser Brown ◽  
Tami Grunewald ◽  
Mary McCormack ◽  
...  
Keyword(s):  
Early Phase ◽  
Clear Cell ◽  
Phase 1 ◽  
Performance Status ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Histological Subtypes ◽  
Prior Therapy ◽  
Early Phase Trials ◽  
Specific Expansion

5597 Background: Patients (pts) with advanced endometrial (EC), cervical and vulval (CVC) cancer have limited therapeutic options and poor prognosis. Early phase trials may be a suitable option for pts with good performance status aided by molecular selection. We sought to determine the outcome of EC and CVC pts treated in a phase 1 unit. Methods: Medical records of pts with EC and CVC treated within an early phase trial between 2010 and 2016 were reviewed. Data comprised pt and tumor characteristics, prior therapy, trial therapy and outcome. Results: 38 pts, median age 59 years (21-74) with EC (19) or CVC (19) were identified. Median prior therapies for advanced disease: 1 (1-3). Histological subtypes: endometrioid (4), high grade serous (HGS 7), carcinosarcoma (CS 4), clear cell (1), and adenosquamous (3) for pts with EC; adenocarcinoma (5), squamous (11), clear cell (2) and neuroendocrine (1) for CVC pts. 20 pts (53%) had Next Generation Sequencing (NGS) using a targeted panel with actionable mutations identified in 10 (KRAS (4), PIK3CA (6) and EGFR (1)). Pts were allocated in order of priority to a trial (1) on the basis of NGS (‘genomic’ 8%), (2) within a ‘tumor specific’ expansion cohort (45%) or (3) a ‘generic’ study (47%). The overall response rate (ORR) was 21% with 34% stable disease (SD) and median progression free survival (PFS) and overall survival (OS) of 11 and 42 weeks respectively, with 10 pts still on study. Within the EC cohort ORR was 21% with 32% SD and PFS and OS of 9 and 38 weeks respectively. For the CVC cohort ORR was 21% with 37% SD and PFS and OS of 12 and 42 weeks respectively. Outcomes were better for the pts in the genomic and tumour specific groups. Both PFS and OS were longer with median PFS of 42, 32 and 8 weeks and OS of 91, not reached and 37 weeks for genomic, tumor specific and generic trials respectively. Conclusions: Early phase trials represent a good option for pts with advanced EC and CVC with meaningful clinical benefit observed even in this small cohort. Encouraging RR and PFS were observed in these pts with limited standard treatment options. This includes pts with difficult to treat histological subtypes such as HGS and CS EC and clear cell and adenocarcinoma CVC. NGS is feasible in real time and increasing use may benefit pts further.

Costs comparison of the immune check point inhibitors versus survival ratio in first-line non-small lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21050-e21050
Author(s):  
Helmy M. Guirgis
Keyword(s):  
Lung Cancer ◽  
Death Receptor ◽  
Survival Ratio ◽  
Check Point ◽  
First Line ◽  
Unresectable Stage ◽  
Programmed Death ◽  
Check Point Inhibitors ◽  
Death Receptor Ligand ◽  
One Year

e21050 Background: Five-year overall survival (OS) was reported in 20% of patients treated by Pembrolizumab (Pembro) in 1st-line advanced/metastatic (a/m)-non-small lung cancer (nsLC). Costs of the immune check point inhibitors (ICI) are relatively high and bound to increase with extended use. We purposed to weigh and compare costs of ICI vs outcome. Methods: OS, hazard ratio (HR) and survival ratio (SR) defined as (1.0-HR) were used. Chemo-drug excluded; costs were calculated in US$. Results: Adjuvant Durv one-year costs in unresectable stage III were $130,956, OS gain 363 days and SR 0.47. Pembro one-year costs were $134,778. OS were 474 and SR 0.37 in programmed death receptor-ligand-1 > 50%. At 5 years, costs were $673,890. Costs of 35-cycle Pembro combination were $336,945, OS 339 and SR 0.51. Costs increased with extended use. Atezolizumab/Bevacizumab-combination (Atezo/Bev) costs x 2-years were $492,114, OS 135 and SR 0.22. Using Biosimilar Bev costs dropped to $429,744. Ipilimumab/Nivolumab (Ipi/Nivo) costs x 2 were $544,696, OS 141 and SR 0.34. Costs of both Atezo/Bev and Ipi/Nivo increased by 50% with one year of extended use. Costs of Pembro-combination were 0.78 lower than Atezo/Bev and 0.62 than Ipi/Nivo. Pembro SR were 2.32 higher than Atezo/Bev and 1.65 than Ipi/Nivo. Absence of direct comparison, however, cast doubts on Pembro advantage. Conclusions: Costs of one-year adjuvant Durv, 3-year Pembro and 35-cycle Pembro-combination were considered fair and equitable with their corresponding SR. Pembro-combination costs were cheaper than Atezo/Bev and Nivo/Ipi. Costs of all drugs and combinations multiplied with extended use.

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