scholarly journals Plasmacytoid urothelial carcinoma (PUC): Imaging features with histopathological correlation

2017 ◽  
Vol 11 (1-2) ◽  
pp. 50 ◽  
Author(s):  
Andrew D. Chung ◽  
Nicola Schieda ◽  
Trevor A. Flood ◽  
Ilias Cagiannos ◽  
Kien T. Mai ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Imaging Finding ◽  
Primary Tumour ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Residual Tumour ◽  
Imaging Features ◽  
Curative Surgery ◽  
Histopathological Correlation ◽  
Peritoneal Spread

Introduction: Plasmacytoid urothelial carcinoma (PUC) is a highgrade variant of conventional urothelial cell carcinoma. This study is the first to describe the imaging findings of PUC, which are previously unreported, using clinical and histopathological correlation. Methods: With internal review board approval, we identified 22 consecutive patients with PUC from 2007‒2014. Clinical parameters, including age, gender, therapy, surgical margins, and longterm outcome, were recorded. Baseline imaging was reviewed by an abdominal radiologist who evaluated for tumour detectability/ location/morphology, local staging, and presence/location of metastases. Pelvic peritoneal spread of tumour (defined as >5mm thick soft tissue spreading along fascial planes) was also evaluated. Followup imaging was reviewed for presence of local recurrence or metastases.Results: Median age at presentation was 74 years (range 51‒86), with only three female patients. Imaging features of the primary tumour in this study were not unique for PUC. Muscle-invasive disease was present on pathology in 19/22 (86%) of tumours, with distant metastases in 2/22 (9%) at baseline imaging. Pelvic peritoneal spread of tumour was radiologically present in 4/20 (20%) at baseline. During followup, recurrent/residual tumour was documented in 16/22 (73%) patients and 7/16 (44%) patients eventually developed distant metastases. Median time to disease recurrence in patients who underwent curative surgery was three months (range 0‒19).Conclusions: PUC is an aggressive variant of urothelial carcinoma with poor prognosis. Pelvic peritoneal spread of tumour as thick sheets extending along fascial planes may represent a characteristic imaging finding of locally advanced PUC.

scholarly journals A comparison between computerised tomography and magnetic resonance imaging in the primary staging of bladder cancer as compared to final histology

2018 ◽  
Vol 12 (1) ◽  
pp. 5-14
Author(s):  
Simon Robinson ◽  
Assad Farooq ◽  
Marc Laniado ◽  
Seema Agrawalla ◽  
Ali Hassan ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Primary Tumour ◽  
Locally Advanced ◽  
Subsequent Treatment ◽  
Nodal Staging ◽  
Resonance Imaging ◽  
Curative Surgery ◽  
Staging Accuracy ◽  
Better Than

Introduction: Accurate and effective imaging to determine the stage of the primary tumour is crucial in deciding whether patients should be treated conservatively, or with surgical or radiochemotherapeutic treatment. There are still concerns about the staging accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) scanners. Methods: We conducted a retrospective analysis of 254 single-surgeon radical cystectomies on a population destined for potentially curative surgery (without evidence of metastatic disease) over 14 years. We compared the staging accuracy of 245 CT scans against 62 conventional T2-weighted MRI scans and compared them to the absolute gold standard, histological analysis using the TNM staging system. Results: Overall, when comparing all the scanner results from 1999 to 2016, the following was observed: • MRI initially appears to be better than CT in staging the primary tumour as either localised or locally advanced disease; and • CT is significantly better than MRI for nodal staging. However, when comparing the more recent results using 53 patients who had both CT and MRI prior to operation, from 2005 to 2016, we find CT improves to match MRI in both primary tumour staging and nodal staging with ‘fair’ kappa scores ( p = 0.84). Conclusions: We confirm that MRI is better at staging extravesical disease and CT better at staging localised disease. Regarding primary tumour accuracy, the volume of the tumour has an influence on its correct staging. Regarding nodal accuracy, the presence of extracapsular extension had no influence. Knowing these limitations of the two modalities should enable better counselling of patients, regardless of their subsequent treatment regimen.

Upper urinary tract urothelial carcinomas – our experience

2020 ◽  
Vol 99 (5) ◽  
pp. 219-225
Keyword(s):  
Urinary Tract ◽  
Urothelial Carcinoma ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Upper Urinary Tract ◽  
Radical Nephroureterectomy ◽  
Treatment Results ◽  
Urothelial Carcinomas ◽  
Therapeutic Procedures ◽  
Advanced Stages

Introduction: Urothelial carcinoma is the second most common urological malignancy. Around 5–10% of tumors are found in the upper urinary tract, while almost 90–95% are in the bladder. Methods: Patients of our department diagnosed with upper urinary tract urothelial carcinoma (UTUC) during the period 2014–2018 were included. The frequency, selected therapeutic procedures and treatment results were analyzed. Results: In the last 5 years, 21 patients with UTUC were diagnosed and surgically treated at the Department of Urology, Regional Hospital Nachod. The main surgical approach was nephroureterectomy. Mortality was 28.6% due to the original tumor diagnosis. Urothelial carcinoma of the upper urinary tract was more common in men than in women in our patient group. Conclusion: Unfortunately, urothelial carcinomas of the upper urinary tract are often dealt with only in locally advanced stages or when nodal or distant metastases are present, making any possible administration of adjuvant chemotherapy complicated as it fails to provide a sufficient effect. Therefore, radical nephroureterectomy remains the gold standard for more than a half of patients. Overall survival depends largely on the presence of distant metastases. The pT category is the major influencing parameter for a relapse.

Post-operative radiation therapy for advanced-stage oropharyngeal cancer

2002 ◽  
Vol 116 (11) ◽  
pp. 920-924 ◽  
Author(s):  
Eric Hansen ◽  
Kathryn Panwala ◽  
John Holland
Keyword(s):  
Radiation Therapy ◽  
Oropharyngeal Cancer ◽  
Primary Tumour ◽  
Locally Advanced ◽  
Distant Metastases ◽  
High Rate ◽  
Advanced Stage ◽  
Combined Surgery ◽  
Regional Control ◽  
Local Regional Control

Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8–2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.

428 Interim analysis of Phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma (mBCC) who progressed on or are intolerant to hedgehog inhibitors (HHIs)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A453-A453
Author(s):  
Karl Lewis ◽  
Ketty Peris ◽  
Aleksandar Sekulic ◽  
Alexander Stratigos ◽  
Lara Dunn ◽  
...  
Keyword(s):  
Cell Carcinoma ◽  
Interim Analysis ◽  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Good Clinical Practice ◽  
Phase 2 ◽  
Curative Surgery ◽  
Pivotal Phase ◽  
Study Protocols

BackgroundHHIs, vismodegib and sonidegib, are approved for treatment of patients with mBCC or locally advanced BCC who are not candidates for surgery or radiation. There is no approved option for patients who progress on or are intolerant to HHIs. Cemiplimab is an anti-programmed cell death-1 monoclonal antibody approved for treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. Here we present the prespecified interim analysis of the mBCC cohort from the pivotal Phase 2, non-randomized, multi-center study of cemiplimab in patients with advanced BCC who discontinued HHI therapy due to disease progression, intolerance, or no better than stable disease after 9 months (NCT03132636).MethodsPatients with mBCC (nodal and/or distant) received cemiplimab 350 mg intravenously every 3 weeks; interim analysis included patients with the opportunity to be followed for approximately 57 weeks. The primary endpoint was objective response rate (ORR) per independent central review (ICR). Secondary objectives included assessment of safety and tolerability, estimation of duration of response (DOR), progression-free survival (PFS), and overall survival (OS).ResultsIn this interim efficacy analysis of 28 patients, 82.1% were males and median age was 65.5 years (range 38−90). Six patients had a partial response, per ICR, for an ORR of 21.4% (95% CI, 8.3, 41.0). ORR per investigator assessment was 28.6% (95% CI, 13.2, 48.7). Among responders, observed DOR was 9−23 months. Median time to response per ICR was 3.2 months (range, 2.1−10.5). Median Kaplan–Meier (KM) estimation of PFS was 8.3 months. Median DOR had not been reached and median KM estimation of OS was 25.7 months. All six responses had observed durations of at least 8 months. The disease control rate was 67.9% (95% CI, 47.6, 84.1).The most common treatment emergent adverse events (TEAEs) regardless of attribution were fatigue (50.0%), diarrhea (35.7%), pruritus (25.0%), and constipation (25.0%). Hypertension (n=2) was the only Grade ≥3 TEAE regardless of attribution occurring in ≥2 patients. TEAEs leading to death occurred in one (3.6%) patient who died from staphylococcal pneumonia, considered unrelated to study treatment.ConclusionsThis interim analysis demonstrates that cemiplimab is the first agent to provide clinically meaningful anti-tumor activity, including durable responses, in patients with mBCC after progression or intolerance on HHI therapy.AcknowledgementsEditorial acknowledgment: Medical writing support was provided by Cindi Hoover, PhD of Prime, Knutsford, UK, funded by Regeneron Pharmaceuticals, Inc. and Sanofi.Ethics ApprovalThe study protocols and all amendments were approved by the institutional review board at each participating study site. The study was conducted in accordance with the principles of the Declaration of Helsinki and with Good Clinical Practice guidelines as defined by the International Conference on Harmonization. All patients provided written informed consent before enrollment.

281 JAVELIN Medley VEGF: phase 2 study of avelumab + axitinib in patients with previously treated non-small cell lung cancer (NSCLC) or treatment naive, cisplatin-ineligible urothelial cancer (UC)

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A307-A307
Author(s):  
Gabriella Galffy ◽  
Iwona Lugowska ◽  
Elena Poddubskaya ◽  
Byoung Chul Cho ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Maintenance Treatment ◽  
Locally Advanced ◽  
Small Cell Lung ◽  
Open Label ◽  
Platinum Based Chemotherapy ◽  
Open Label Phase ◽  
Treatment Naïve ◽  
Previously Treated ◽  
Grade 3

BackgroundAvelumab, a human anti–PD-L1 monoclonal antibody, has shown a manageable safety profile and antitumor activity in multiple tumor types, including platinum-resistant metastatic or recurrent NSCLC,1 and is approved for patients with locally advanced or metastatic UC who have progressed after ≥1 previous line of platinum-based chemotherapy2 3 and as maintenance treatment for those who have not progressed with platinum-based chemotherapy.4 JAVELIN Medley VEGF (NCT03472560) evaluated the efficacy and safety of avelumab + axitinib, a potent inhibitor of VEGFR 1, 2, and 3, in patients with advanced or metastatic NSCLC or UC.MethodsEligible patients with NSCLC had received ≥1 prior platinum-containing therapy and ≤2 prior lines of systemic therapy for locally advanced or metastatic disease; patients with UC were treatment naive in the locally advanced or metastatic setting and ineligible for cisplatin-containing chemotherapy. Patients were immune checkpoint inhibitor naïve and received avelumab 800 mg intravenously every 2 weeks + axitinib 5 mg orally twice daily. The primary endpoint was confirmed objective response (OR) per investigator assessment (RECIST 1.1). Secondary endpoints included progression-free survival (PFS) and safety. PD-L1 expression was assessed in baseline tumor samples (Ventana SP263 assay). Data have not undergone standard quality checks and are subject to change due to COVID-19–related healthcare burden.ResultsA total of 41 patients with NSCLC and 20 with UC received avelumab + axitinib. The confirmed OR rate was 31.7% (95% CI, 18.1–48.1) in the NSCLC cohort and 10% (95% CI, 1.2–31.7) in the UC cohort (all partial responses); 16 patients (39.0%) and 5 (25.0%) had stable disease, respectively. Responses were observed regardless of PD-L1 expression status. Median PFS was 5.5 months (95% CI, 2.5–7.0) in the NSCLC cohort and 2.3 months (95% CI, 1.8–5.6) in the UC cohort. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 24 patients (58.5%) in the NSCLC cohort; the most common was hypertension (n=7 [17.1%]). Grade ≥3 TRAEs occurred in 9 patients (45.0%) in the UC cohort; the most common were amylase increased, asthenia, decreased appetite, and palmar-plantar erythrodysesthesia syndrome (n=2 [10%] each). One patient in each cohort experienced a TRAE that led to death (gastric perforation and urinary bladder hemorrhage).ConclusionsAvelumab + axitinib showed antitumor activity and a manageable safety profile in patients with advanced or metastatic NSCLC or UC consistent with findings from studies of each drug alone and in combination.Trial RegistrationNCT03472560Ethics ApprovalThe study was approved by each site’s independent ethics committee.ConsentN/AReferencesGulley JL, Rajan A, Spigel DR, et al. Avelumab for patients with previously treated metastatic or recurrent non-small-cell lung cancer (JAVELIN Solid Tumor): dose-expansion cohort of a multicentre, open-label, phase 1b trial. Lancet Oncol 2017;18:599–610.Patel MR, Ellerton J, Infante JR, et al. Avelumab in metastatic urothelial carcinoma after platinum failure (JAVELIN Solid Tumor): pooled results from two expansion cohorts of an open-label, phase 1 trial. Lancet Oncol 2018;19:51–64.Bavencio(avelumab) injection. [package insert] Darmstadt, Germany: Merck KGaA; 2019.US Food and Drug Administration. FDA approves avelumab for urothelial carcinoma maintenance treatment. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-avelumab-urothelial-carcinoma-maintenance-treatment. Accessed August 19, 2020.

scholarly journals Polymorphisms in the Gene Encoding Caspase 8 May Predict the Response to First-Line Platinum-Based Chemotherapy in Locally Advanced or Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 10 (5) ◽  
pp. 1126
Author(s):  
Michał Szczyrek ◽  
Radosław Mlak ◽  
Aneta Szudy-Szczyrek ◽  
Karolina Kędziora ◽  
Teresa Małecka-Massalska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Locally Advanced ◽  
Distant Metastases ◽  
Small Cell ◽  
Caspase 8 ◽  
Small Cell Lung ◽  
Gene Encoding ◽  
Platinum Based Chemotherapy

Caspase 8 is a protein involved in the process of cell apoptosis, which may affect the efficacy of anti-cancer treatment. The aim of our study was to determine the impact of polymorphisms in the CASP-8 gene encoding caspase 8 on the prognosis in non-small-cell lung cancer (NSCLC). The study involved 99 patients with newly diagnosed locally advanced or metastatic NSCLC treated with platinum-based chemotherapy. The presence of the GG genotype was associated with distant metastases, smoking, and a family history of cancer. The higher risk of early progression was associated with weight loss and the CASP-8 genotype (GG vs. AG or AA: 20.51% vs. 2.86%). The higher risk of progression-free survival (PFS) shortening was associated with a higher stage of disease (hazard ratio (HR) = 2.50, 95% CI: 1.61–3.89, p < 0.0001), distant metastases (HR = 2.30, 95% CI: 1.42–3.72, p = 0.0016), and the GG genotype (HR = 1.68, 95% CI: 1.10–2.57, p = 0.0152). The influence of the GG genotype on the PFS was confirmed in a multivariate analysis (HR = 1.80, 95% CI: 1.06–3.05, p = 0.0317). We did not confirm the influence of CASP-8 genotypes on the overall survival (OS).

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