Correlation between depression/anxiety and somatic circulating tumor DNA (ctDNA) alterations in patients with metastatic renal cell carcinoma (mRCC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 649-649
Author(s):  
Cristiane Decat Bergerot ◽  
Paulo Gustavo Bergerot ◽  
Karen L. Clark ◽  
Matthew J. Loscalzo ◽  
Richard B. Lanman ◽  
...  
Keyword(s):  
Clear Cell ◽  
Clinical Care ◽  
Psychological Disorders ◽  
Psychosocial Interventions ◽  
Circulating Tumor Dna ◽  
Depression And Anxiety ◽  
Medication History ◽  
Genomic Alterations ◽  
Number Range ◽  
Entire Cohort

649 Background: A correlation between depression/anxiety and survival has been established in patients (pts) with mRCC (Cohen et al PLoS One 2012). We hypothesize that frequently encountered genomic alterations (GAs) in mRCC may identify pts with these psychological disorders. Methods: Data was obtained from pts with mRCC who received ctDNA profiling as a part of routine clinical care at progression using a CLIAA-certified platform evaluating 73 genes. Genomic alterations (GAs) were pooled for the entire cohort. ICD-9 diagnoses corresponding to anxiety and depression (300 and 311, respectively) were derived from detailed chart review, including review of established diagnoses and medication history. The chi-square test was used to determine the association between frequent GAs (those occurring in ≥5% of the study population) and the presence of depression and anxiety. Results: ctDNA results from 52 pts with mRCC were assessed (gender: 69.2% M, 30.8% F; average age: 58; histology: 84.6% clear cell, 15.4% non-clear cell). The most commonly used 1st-line treatment was sunitinib (46.1%). GAs were detected in 55.8% of pts. The most frequent GAs in the overall cohort included TP53 (21.1%), VHL (17.3%) and EGFR (7.7%). 5 and 8 pts were coded as having depression and anxiety, respectively. The average number (range) of ctDNA alterations detected was 1.1 (0-4) in patients with depression/anxiety and 1.6 (0-10) in those without (P = 0.001). The presence of VHL mutation was found to occur exclusively in pts with no depression/anxiety (P = 0.05), while 13 patients (25%) lacking VHL GAs had these psychological disorders. Conclusions: The absence of VHL alterations have been associated with poorer survival in pts with RCC (Patard et al Int J Cancer 2008), and our findings suggest that these patients may further have higher rates of depression/anxiety. Our data imply that patients bearing mutations in VHL may a prime target for early psychosocial interventions.

Evolution of circulating tumor DNA (ctDNA) profile from first-line (1L) to second-line (2L) therapy in metastatic renal cell carcinoma (mRCC).

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 434-434 ◽  
Author(s):  
Sumanta K. Pal ◽  
Guru Sonpavde ◽  
Neeraj Agarwal ◽  
Nicholas J. Vogelzang ◽  
Sandy Srinivas ◽  
...  
Keyword(s):  
Practice Patterns ◽  
Clear Cell ◽  
Selective Pressure ◽  
Clinical Care ◽  
Circulating Tumor Dna ◽  
Mechanisms Of Resistance ◽  
First Line ◽  
Number Range ◽  
Entire Cohort ◽  
Tumor Dna

434 Background: Treatment of mRCC typically entails mechanistically distinct agents across the 1L and 2L setting. Activity of these agents may be predicated on selective pressure that modulates RCC biology. ctDNA is a platform to conveniently ascertain temporal changes in genomic profile. Methods: Data was obtained from pts with mRCC who received ctDNA profiling as a part of routine clinical care at progression using a CLIAA-certified platform evaluating 70 genes. Genomic alterations (GAs) were pooled for the entire cohort. A comparison of 1L vs. 2L was performed, with grouping based on conventional practice patterns (1L regimens included sunitinib, pazopanib and bevacizumab, and 2L regimens included everolimus, axitinib, cabozantinib, and nivolumab). Results: ctDNA results from 224 pts with mRCC were assessed (gender: 149 M, 75 F; average age: 62; histology: 89 clear cell, 37 non-clear cell, 98 unknown). GAs were detected in 78.6% of pts. The most frequent GAs in the overall cohort included TP53 (35%), VHL (23%), EGFR (17%), NF1 (16%), and ARID1A (12%). 64 and 56 pts were coded as receiving 1L and 2L agents, respectively. The average number (range) of ctDNA alterations detected was 2.9 (1-14) in 1L and 3.7 (1-16) in 2L with median (range) ctDNA variant allele fractions of 0.23 (0.05-9.92) in 1L and 0.24 (0.04-47.14) in 2L. The highest disparity in GA frequencies in 2L vs. 1L were in TP53 (49% vs. 25%), VHL (29% vs. 25%), NF1 (20% vs. 15%), EGFR (17% vs. 21%), and PIK3CA (17% vs. 8%). Isolating 2L pts who specifically had 1L VEGF-therapy documented, these differences were even more prominent in comparison to 1L pts: TP53 (64% vs. 31%), PIK3CA (29% vs. 8%), and NF1 (29% vs. 4%). Conclusions: In the largest assessment of ctDNA in mRCC to date, the majority of pts demonstrated clinically relevant GAs. Increasing p53 and mTOR pathway (e.g, NF1, PIK3CA) alteration in 2L pts with 1L VEGF-directed therapy may underlie mechanisms of resistance. Increasing GA frequency from 1L to 2L pts may have implications for immunotherapeutic approaches.

Association of somatic mutational burden with depression and anxiety in patients with metastatic urothelial cancer (mUC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 471-471
Author(s):  
Cristiane Decat Bergerot ◽  
Karen L. Clark ◽  
Paulo Gustavo Bergerot ◽  
Kimlin Tan Ashing ◽  
Andrew W Hahn ◽  
...  
Keyword(s):  
Clinical Care ◽  
Adjustment Disorder ◽  
High Rate ◽  
Cumulative Number ◽  
Depression And Anxiety ◽  
Medication History ◽  
Entire Cohort ◽  
Mutational Burden ◽  
Metastatic Urothelial Cancer ◽  
Significant Difference

471 Background: Depression and anxiety are highly prevalent in patients (pts) with genitourinary tumors, including UC (Yang et al PLoS ONE 2016). Given that mUC has a high rate of somatic genomic alterations (GAs), we sought to determine if tumor mutational burden (TMB) or specific alterations were related to the incidence of these psychiatric disorders. Methods: From a single institution, we identified consecutive pts with mUC who had comprehensive genomic profiling done in the course of routine clinical care. In a CLIA-certified laboratory, DNA was extracted from 40 microns of FFPE sections. Hybridization-captured, adaptor ligation based libraries were used to a mean coverage depth of 718X for up to 315 cancer-related genes plus introns from up to 28 genes frequently rearranged in cancer. TMB was estimated based on the cumulative number of GAs. ICD-9 diagnoses corresponding to adjustment disorder (309.28), anxiety (300) and depression (311) were derived from detailed chart review, including review of established diagnoses and medication history. Results: A total of 43 pts (74.4% M / 25.6% F) were assessed with a median age of 65.5 (range, 49-81). Formal diagnoses of adjustment disorder, anxiety and depression were noted in 16.3%, 9.3% and 7.0% pts, respectively. An average of 6.3 GAs/pt (range, 0-14) were observed over the entire cohort. The rate of GA was higher in pts with anxiety vs adjustment disorder or depression (8.5 vs 6.8 or 4.0, P=0.01). No significant difference was observed in adjustment disorder or depression based on the frequency of GAs. GAs in BAP1, PIK3CB, NOTCH1, ALK, CDH1 and FANCC were noted to be associated with higher rates of anxiety (P=0.02). Similarly, GAs in FGFR1 was noted to be associated with higher rates of depression (P=0.002) and in CHEK2 in depression and adjustment disorder (P=0.03). Conclusions: Our study represents the first pyschogenomic analysis of pts with mUC. While higher TMB has been associated with favorable prognosis (Isharwal et al EU Focus 2017), we paradoxically found this to be related to higher rates of anxiety. Our findings suggest that genomically selected subsets of patients may be prime candidates for early psychosocial screening and intervention.

scholarly journals A convention-radiomics CT nomogram for differentiating fat-poor angiomyolipoma from clear cell renal cell carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yanqing Ma ◽  
Weijun Ma ◽  
Xiren Xu ◽  
Zheng Guan ◽  
Peipei Pang
Keyword(s):  
Risk Factors ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Logistic Model ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma ◽  
Entire Cohort ◽  
Conventional Ct ◽  
Radiomics Signature

AbstractThis study aimed to construct convention-radiomics CT nomogram containing conventional CT characteristics and radiomics signature for distinguishing fat-poor angiomyolipoma (fp-AML) from clear-cell renal cell carcinoma (ccRCC). 29 fp-AML and 110 ccRCC patients were enrolled and underwent CT examinations in this study. The radiomics-only logistic model was constructed with selected radiomics features by the analysis of variance (ANOVA)/Mann–Whitney (MW), correlation analysis, and Least Absolute Shrinkage and Selection Operator (LASSO), and the radiomics score (rad-score) was computed. The convention-radiomics logistic model based on independent conventional CT risk factors and rad-score was constructed for differentiating. Then the relevant nomogram was developed. Receiver operation characteristic (ROC) curves were calculated to quantify the accuracy for distinguishing. The rad-score of ccRCC was smaller than that of fp-AML. The convention-radioimics logistic model was constructed containing variables of enhancement pattern, VUP, and rad-score. To the entire cohort, the area under the curve (AUC) of convention-radiomics model (0.968 [95% CI 0.923–0.990]) was higher than that of radiomics-only model (0.958 [95% CI 0.910–0.985]). Our study indicated that convention-radiomics CT nomogram including conventional CT risk factors and radiomics signature exhibited better performance in distinguishing fp-AML from ccRCC.

scholarly journals Dietary intake of branched-chain amino acids in relation to depression, anxiety and psychological distress

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Glareh Koochakpoor ◽  
Asma Salari-Moghaddam ◽  
Ammar Hassanzadeh Keshteli ◽  
Hamid Afshar ◽  
Ahmad Esmaillzadeh ◽  
...  
Keyword(s):  
Amino Acids ◽  
Psychological Distress ◽  
Dietary Intake ◽  
Psychological Disorders ◽  
Branched Chain Amino Acids ◽  
Inverse Association ◽  
Depression And Anxiety ◽  
Lower Odds ◽  
Significant Inverse Association ◽  
Branched Chain

Abstract Background There is no previous study that examined the association between branched-chain amino acids (BCAAs) intake and odds of psychological disorders. The aim of this study was to investigate the association between dietary BCAAs and odds of psychological disorders including depression, anxiety, and psychological distress in a large sample of Iranian adults. Methods In this cross-sectional study on 3175 Iranian adults aged 18–55 years, a validated food frequency questionnaire was used to assess dietary intakes. BCAAs intake was computed by summing up the amount of valine, leucine, and isoleucine intake from all food items in the questionnaire. Psychological health was examined through the use of Iranian validated version of the Hospital Anxiety and Depression Scale (HADS). Psychological distress was assessed using General Health Questionnaire (GHQ). For depression and anxiety, scores of 8 or more on either subscale were considered as psychological disorders and scores of 0–7 were defined as “normal”. In terms of psychological distress, the score of 4 or more was defined as psychological distress. Results Mean age of study participants was 36.2 ± 7.8 years. Overall, 26.4% (n = 837) of study subjects had depression, 11.9% (n = 378) had anxiety and 20.9% (n = 665) were affected by psychological distress. After controlling for potential confounders, participants in the highest tertile of total BCAAs intake had lower odds of depression (OR: 0.76; 95% CI: 0.60–0.96) and anxiety (OR: 0.66; 95% CI: 0.47–0.91) compared with those in the lowest tertile. Participants in the top tertile of valine intake had a lower odds of depression (OR: 0.76; 95% CI: 0.60–0.96) and anxiety (OR: 0.65; 95% CI: 0.47–0.90) compared with those in the bottom tertile. A significant inverse association was also seen between leucine intake and depression (OR: 0.77; 95% CI: 0.61–0.98) and anxiety (OR: 0.66; 95% CI: 0.47–0.91). In addition, a significant inverse association was observed between isoleucine intake and odds of depression (OR: 0.75; 95% CI: 0.59–0.95) and anxiety (OR: 0.62; 95% CI: 0.45–0.86). There was no significant association between isoleucine intake and odds of psychological distress. Conclusion Evidence indicating an inverse association between dietary intake of BCAAs and odds of depression and anxiety was found. Prospective studies are required to confirm these findings.

scholarly journals Emotion regulation therapy for cancer caregivers—an open trial of a mechanism-targeted approach to addressing caregiver distress

2018 ◽  
Vol 10 (2) ◽  
pp. 413-422 ◽  
Author(s):  
Allison J Applebaum ◽  
Aliza A Panjwani ◽  
Kara Buda ◽  
Mia S O’Toole ◽  
Michael A Hoyt ◽  
...  
Keyword(s):  
Emotion Regulation ◽  
Caregiver Burden ◽  
Psychosocial Interventions ◽  
Anxiety Symptoms ◽  
Open Trial ◽  
Self Report ◽  
Central Feature ◽  
Depression And Anxiety ◽  
Before And After ◽  
Clinically Significant

Abstract Informal caregivers (ICs) are integral to care provided to patients facing life-threatening or incurable illnesses. This responsibility causes considerable burden, as approximately one half of ICs report clinically significant symptoms of depression and/or anxiety that persist when left untreated. Psychosocial interventions containing efficacious treatment principles (e.g., cognitive behavior therapy [CBT]) show disappointing results in reducing anxiety and depression in ICs. This may reflect failure of these interventions to specifically target crucial mechanisms underlying the central feature of distress caused by the patient’s illness—notably, perseverative negative thinking (PNT). Emotion Regulation Therapy (ERT) is an efficacious CBT developed to explicitly target mechanisms underlying PNT and the emotional concomitants that arise in response to stressful situations. This open trial was conducted to evaluate the acceptability and initial efficacy of ERT adapted to the experience of cancer ICs (ERT-C). Thirty-one ICs provided informed consent and completed eight weekly individual sessions of ERT-C. Participants completed self-report measures of depression and anxiety symptoms, PNT, emotion regulation deficits, and caregiver burden before and after treatment. ERT-C was well tolerated as indicated by 22 treatment completers and feedback provided in exit interviews. ICs demonstrated reduced depression and anxiety symptoms, PNT, and emotion regulation deficits with moderate to large effect sizes (Hedge’s g range: 0.36–0.92). Notably, caregiver burden was not reduced but ICs expressed more ability to confront caregiving-related challenges. Findings offer promising but preliminary support for ERT-C as a conceptual model and treatment modality for distressed cancer ICs.

scholarly journals Genomic Alterations and Outcomes with VEGF-Targeted Therapy in Patients with Clear Cell Renal Cell Carcinoma

Kidney Cancer ◽  
2017 ◽  
Vol 1 (1) ◽  
pp. 49-56 ◽  
Author(s):  
M.I. Carlo ◽  
B. Manley ◽  
S. Patil ◽  
K.M. Woo ◽  
D.T. Coskey ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Genomic Alterations ◽  
Cell Renal Cell Carcinoma

scholarly journals PATH-06. ASSESSMENT OF CIRCULATING TUMOR DNA IN CEREBROSPINAL FLUID BY WHOLE EXOME SEQUENCING TO DETECT GENOMIC ALTERATIONS OF GLIOBLASTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii165-ii165
Author(s):  
Hao Duan ◽  
Zhenqiang He ◽  
Zhenghe Chen ◽  
Yonggao Mou
Keyword(s):  
Cerebrospinal Fluid ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Genomic Alterations ◽  
Tissue Samples ◽  
Whole Exome ◽  
Resected Tumor ◽  
Tumor Dna

Abstract Cerebrospinal fluid (CSF) has been demonstrated as a better source of circulating tumor DNA (ctDNA) than plasma for brain tumors. However, it is unclear whether whole exome sequencing (WES) is qualified for detection of ctDNA in CSF. The aim of this study was to determine if assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma. CSFs of ten glioblastoma patients were collected pre-operatively at the Department of Neurosurgery, Sun Yat-sen University Cancer Center. ctDNA in CSF and genome DNA in the resected tumor were extracted and subjected to WES. The identified glioblastoma-associated mutations from ctDNA in CSF and genome DNA in the resected tumor were compared. Due to the ctDNA in CSF was unqualified for exome sequencing for one patient, nine patients were included into the final analysis. More glioblastoma-associated mutations tended to be detected in CSF comparing with the corresponding tumor tissue samples (3.56±0.75 vs. 2.22±0.32, P=0.097), while the statistical significance was limited by the small sample size. The average mutation frequencies were similar in CSF and tumor tissue samples (74.12% ± 6.03% vs. 73.83% ± 5.95%, P = 0.924). The R132H mutation of isocitrate dehydrogenase 1 and the G34V mutation of H3F3A which had been reported in the pathological diagnoses were also detected from ctDNA in CSF by WES. Patients who received temozolomide chemotherapy previously or those whose tumor involved subventricular zone tended to harbor more mutations in their CSF. Assessment of ctDNA in CSF by WES is a feasible approach to detect genomic alterations of glioblastoma, which may provide useful information for the decision of treatment strategy.

scholarly journals The Landscape of Actionable Genomic Alterations in Cell-Free Circulating Tumor DNA from 21,807 Advanced Cancer Patients

2018 ◽  
Vol 24 (15) ◽  
pp. 3528-3538 ◽  
Author(s):  
Oliver A. Zill ◽  
Kimberly C. Banks ◽  
Stephen R. Fairclough ◽  
Stefanie A. Mortimer ◽  
James V. Vowles ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Advanced Cancer ◽  
Circulating Tumor Dna ◽  
Advanced Cancer Patients ◽  
Genomic Alterations ◽  
Tumor Dna

Circulating tumor DNA (ctDNA) in patients with advanced adrenocortical carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4585-4585
Author(s):  
Bassel Nazha ◽  
Hiba I. Dada ◽  
Leylah Drusbosky ◽  
Jacqueline T Brown ◽  
Deepak Ravindranathan ◽  
...  
Keyword(s):  
Adrenocortical Carcinoma ◽  
Treatment Options ◽  
Genomic Data ◽  
Circulating Tumor Dna ◽  
Copy Number Variations ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Entire Cohort ◽  
Genomic Landscape ◽  
Ctdna Analysis

4585 Background: Adrenocortical Carcinoma (ACC) is a rare and aggressive malignancy with poor prognosis and limited treatments in the advanced setting. Molecular pathways with tumor suppressor genes (e.g. TP53, CDKN2A) and oncogenes (e.g. CTNNB1 and RAS) are implicated in oncogenesis. To our knowledge, the genomic landscape of ctDNA alterations for ACC has not been described in a large cohort. We report plasma-based ctDNA alterations in patients with advanced ACC. Methods: We retrospectively evaluated genomic data from 102 patients with ACC who had ctDNA testing between 12/2016 – 10/2020 using Guardant360 (Guardant Health, CA). ctDNA analysis interrogated single nucleotide variants (SNV), fusions, indels and copy number variations (CNV) of up to 83 genes. We evaluated the frequency of genomic alterations, the landscape of co-occurring mutations, and pathogenic or likely pathogenic alterations with potential targeted therapies. The prevalence of alterations identified in ctDNA were compared to those detected in tissue using a publicly available database (cBioPortal). Results: The median age was 54 years (range 24-81), and 55% of patients were male. Among the entire cohort, 84 pts (82.4%) had ≥1 somatic alteration detected. Mutations were most frequently detected in TP53 (52%), EGFR (23%), CTNNB1 (18%), MET (18%), and ATM (14%). The frequencies detected in ctDNA were similar to the results detected in tissue. Pathogenic and/or likely pathogenic mutations in therapeutically relevant alterations were observed in 36 patients (35%), including EGFR, BRAF, MET, CDKN2A, and CDK4/6 (Table 1). The most frequently co-occurring mutations were EGFR + TP53 (14%), EGFR + MET (11%), BRAF + MET (10%). Conclusions: Blood-based ctDNA profiling in advanced ACC provided comprehensive genomic data in most patients, with a similar profile to tumor tissue analyses. Over one third of patients had actionable mutations with approved therapies in other cancers. This approach might inform the development of personalized treatment options for this aggressive malignancy.[Table: see text]

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