Early cancer cachexia phenotype predicts survival of advanced urothelial cancer patients treated with pembrolizumab

2021 ◽  
Author(s):  
Shumpei Yamamoto ◽  
Hiroshi Fukushima ◽  
Shohei Fukuda ◽  
Sho Uehara ◽  
Yosuke Yasuda ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Cachexia ◽  
Urothelial Cancer ◽  
Early Cancer ◽  
Advanced Urothelial Cancer

scholarly journals Transcriptional Profiling of Advanced Urothelial Cancer Predicts Prognosis and Response to Immunotherapy

2020 ◽  
Vol 21 (5) ◽  
pp. 1850 ◽  
Author(s):  
Seung-Woo Baek ◽  
In-Hwan Jang ◽  
Seon-Kyu Kim ◽  
Jong-Kil Nam ◽  
Sun-Hee Leem ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Survival Analysis ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Urothelial Cancer ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Prognostic Impact ◽  
T Effector Cells ◽  
Advanced Urothelial Cancer

Recent investigations reported that some subtypes from the Lund or The Cancer Genome Atlas (TCGA) classifications were most responsive to PD-L1 inhibitor treatment. However, the association between previously reported subtypes and immune checkpoint inhibitor (ICI) therapy responsiveness has been insufficiently explored. Despite these contributions, the ability to predict the clinical applicability of immune checkpoint inhibitor therapy in patients remains a major challenge. Here, we aimed to re-classify distinct subtypes focusing on ICI responsiveness using gene expression profiling in the IMvigor 210 cohort (n = 298). Based on the hierarchical clustering analysis, we divided advanced urothelial cancer patients into three subgroups. To confirm a prognostic impact, we performed survival analysis and estimated the prognostic value in the IMvigor 210 and TCGA cohort. The activation of CD8+ T effector cells was common for patients of classes 2 and 3 in the TCGA and IMvigor 210 cohort. Survival analysis showed that patients of class 3 in the TCGA cohort had a poor prognosis, while patients of class 3 showed considerably prolonged survival in the IMvigor 210 cohort. One of the distinct characteristics of patients in class 3 is the inactivation of the TGFβ and YAP/TAZ pathways and activation of the cell cycle and DNA replication and DNA damage (DDR). Based on our identified transcriptional patterns and the clinical outcomes of advanced urothelial cancer patients, we constructed a schematic summary. When comparing clinical and transcriptome data, patients with downregulation of the TGFβ and YAP/TAZ pathways and upregulation of the cell cycle and DDR may be more responsive to ICI therapy.

scholarly journals Validity and performance of the Functional Assessment of Cancer Therapy-Bladder (FACT-Bl) among advanced urothelial cancer patients

2019 ◽  
Vol 27 (11) ◽  
pp. 4189-4198 ◽  
Author(s):  
Arnold Degboe ◽  
Cristina Ivanescu ◽  
Jeffrey M. Rohay ◽  
Ralph R. Turner ◽  
David Cella
Keyword(s):  
Cancer Therapy ◽  
Cancer Patients ◽  
Functional Assessment ◽  
Urothelial Cancer ◽  
Advanced Urothelial Cancer ◽  
And Performance

Single arm phase II study of docetaxel and lapatinib in metastatic urothelial cancer: USC trial 4B-10-4.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 424-424 ◽  
Author(s):  
Sujie Tang ◽  
Tanya B. Dorff ◽  
Denice D Tsao-Wei ◽  
Kristy Massopust ◽  
Charlean Ketchens ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cancer Patients ◽  
Phase Ii ◽  
Urothelial Cancer ◽  
Phase Ii Study ◽  
Palliative Therapy ◽  
Progression Rate ◽  
Stage Design ◽  
Metastatic Urothelial Cancer ◽  
Advanced Urothelial Cancer

424 Background: Advanced urothelial cancer progressing after first line systemic therapy is fatal. No agent in the second line or later setting has demonstrated improved survival although taxanes, pemetrexed, gemcitabine & vinflunine have activity & are used as palliative therapy. The Her2 pathway is up-regulated in some urothelial cancers and Her2 targeted therapy has enhanced chemotherapy effect in other cancers. We tested docetaxel with lapatinib, a Her1/Her2 TKI in urothelial cancer patients. Methods: Pts with measurable or evaluable urothelial cancerentered a single arm 2-stage phase II clinical trial, with PFS rate at 12 weeks as the primary endpoint in a Simon 2-stage design of 14+26 patients. The goal was a 12 week non progression rate of 60% - seen as promising compared to a rate of < 40% seen as not. In a 2-stage design if ≥ 6 of 14 patients had not progressed by 12 weeks the trial would continue to 40 pts. Secondary endpts: ORR, safety & OS. First 6 patients were given lapatinib 1250mg PO daily & docetaxel 60mg/m2 IV q3wk; docetaxel dose then increased to 75mg/m2 q3wk. Tumor tissue & circulating microenvironment were evaluated. Results: From July 2011 to July 2013, 15 pts were accrued. Median age 65 y, male 80%, ECOG 0 73%, Caucasian 73%, Mets: Liver 20%, Lung 20%, Bone 20%. PFS at 12 weeks 40%+/-13% - the trial was terminated after first stage. Reason off therapy: PD 10 (67%), toxicity 4 (27%). RECIST 1.1 best response: CR 1 (8%), SD 4 (31%), PD 8 (62%). Median OS: 6.3 (2.2, 12.7), PFS 2.0 (1.3, 6.6) months; 2 pts alive, follow up at 6.9 & 8.1 months. Common toxicities: diarrhea 80% (gr3 33%), vomiting 40% (gr3 26.7%), nausea 67% (gr3 26.7%) & fatigue 73.3% (gr3 6.7%). Conclusions: This phase II study of docetaxel with lapatinib in advanced urothelial cancer patients failed to provide sufficient efficacy for us to complete full accrual. One patient had a complete response and molecular correlatives may shed light on what may have predisposed to this. Intercurrently, another trial of maintenance lapatinib or placebo after chemotherapy in Her2+ patients reports no benefit (Powles ASCO 2015). Lapatinib alone or in combination is not recommended as therapy in urothelial cancer patients unless new tractable markers of response are developed. Clinical trial information: NCT01382706.

scholarly journals Malnutrition and cancer, diagnosis and treatment

2021 ◽  
Author(s):  
Angelika Beirer
Keyword(s):  
Weight Loss ◽  
Cancer Patients ◽  
Cancer Cachexia ◽  
Screening Tool ◽  
Psychological Treatment ◽  
Early Stage ◽  
Nutritional Therapy ◽  
German Society ◽  
Fat Free Mass ◽  
Nutritional Risk

Summary Background The prevalence of malnutrition in cancer patients ranges from about 20% to more than 70%. However, 10–20% of cancer patients’ deaths are related to malnutrition, not the malignancy itself. To reverse the pattern of weight loss, improve the patients’ quality of life, reduce the treatment toxicity, the psychological stress and the risk of mortality, the diagnosis of malnutrition should be made as early as possible to facilitate the best possible treatment. Methods A systematic literature search was conducted following guidelines of ESPEN (European Society for Clinical Nutrition), DGEM (German Society for Nutritional Medicine) and ASPEN (American Society for Parenteral and Enteral Nutrition). Results and conclusion To assess the risk of malnutrition, all cancer patients should be screened regularly with a valid screening tool (e.g., MUST [Malnutrition Universal Screening Tool], NRS [Nutritional Risk Screening] or PG-SGA [Scored Patient-Generated Subjective Global Assessment]). If risk of malnutrition is present, adequate nutritional therapy is recommended to stop involuntary weight loss. Patients should engage in exercise to maintain and improve muscle mass, strength and function. They should be offered regular dietetic counselling, and their muscle depletion should be monitored by determining fat-free mass. As cachectic patients in particular are at risk, the presence of cachexia should also be recognized at an early stage. Three consensus-based definitions are widely accepted: Fearon et al. and the EPCRC (European Palliative Care Research Collaborative) propose definitions specifically for cancer cachexia, while Evans et al. put forward a definition for cachexia associated with all types of underlying chronic diseases. However, if there is a cancer cachexia diagnosis, additional pharmacological and psychological treatment should be considered.

Sequential therapies for advanced urothelial cancer: Hope meets new challenges

2021 ◽  
pp. 103248
Author(s):  
Daniel Herchenhorn ◽  
Vinicius Freire ◽  
Thamires Oliveira ◽  
Juliana Tarouquella
Keyword(s):  
Urothelial Cancer ◽  
New Challenges ◽  
Advanced Urothelial Cancer
Sign in / Sign up

Export Citation Format

Share Document