Liquid biopsy testing: Impact on treatment assignment and survival in a community-based oncology practice—A real-world experience.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3027-3027
Author(s):  
Khalil Choucair ◽  
Bassam Ibrahim Mattar ◽  
Quoc Van Truong ◽  
Travis Lee Koeneke ◽  
Phu Van Truong ◽  
...  
Keyword(s):  
Liquid Biopsy ◽  
Statistical Significance ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Karnofsky Performance Scale ◽  
Solid Cancer ◽  
Community Practice ◽  
Treatment Assignment ◽  
Match Rate

3027 Background: Liquid biopsy is a promising, rapid and minimally invasive genetic test examining circulating tumor DNA. It offers a significant potential in selecting signal-matched therapeutic options. Methods: A retrospective chart review was conducted on adult patients with advanced solid cancer whose tumors were tested with the Guardant 360® (Guardant Health) assay between December 2018 and 2019. A follow-up analysis (censor date: 01/06/2021) was carried to assess the actual impact of testing results on treatment assignment and survival. Results: A total of 178 patients underwent testing. Mean age at diagnosis was 65 years. Median (m) Karnofsky Performance Scale was 90% and the majority of patients (89.9%) had ≥ stage III-B disease. Lung (LCa; 50.56%), breast (BCa; 17.42%) and colorectal (CRCa; 7.87%) cancers were the most common cancer types. A positive test was reported in 140/178 patients (78.7%); of those, 105/140 (75%) had an actionable mutation, either with an FDA-approved target-matched therapy (n = 32/105; 30.5%) or with a therapy outside current FDA indication (n = 73/105; 69.5%). In patients with no actionable mutation (n = 35/140; 25%), 85.7% (n = 30/35) had a signal-based clinical trial opportunity. The actual overall signal-based matching rate was 17.8% (24/135; vs. 82.2% no-match rate). Within candidates for FDA-approved treatment, 50% (16/32) received targeted therapy while only 6.9% (5/73) were treated with targeted agents outside current FDA indication: mean matching score (number of matched drugs/number of actionable mutations) was 0.6 (range: 0.33-2) and 0.8 (range: 0.17-2), respectively. Only 10% (3/30) were referred to signal-based clinical trials. Survival analysis of LCa, BCa and CRCa patients with actionable mutations who actually received any therapy (n = 66) revealed post-testing survival advantage for target-matched therapy (n = 22) compared to unmatched therapy (n = 44): overall survival (OS) was longer in the matched cohort (mOS: 13.3 months; 95% CI: 11.8-14.8 vs. 10.7 months; 95% CI: 9-12.4 in unmatched) but did not reach statistical significance ( P = 0.09). Progression free survival (PFS) was significantly longer in patients who received matched therapy (mPFS: 11.3 months; 95% CI: 9.9-12.7 vs. mPFS: 6.8 months; 95% CI: 5.1-8.5 in unmatched; P < 0.05). Conclusions: Implementation of liquid biopsy testing is feasible in community practice and impacts therapeutic choices in patients with advanced malignancies. Receipt of liquid biopsy-generated signal-matched precision therapies conferred added survival benefit compared to unmatched therapy. Larger sample size studies are needed to validate these findings.

Correlation of in vitro chemotherapy drug resistance assay to clinical response to carboplatin and paclitaxel combination chemotherapy in ovarian carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16546-e16546
Author(s):  
Kit Cheng ◽  
Iuliana Shapira ◽  
Lisa M Rosen ◽  
Veena S. John ◽  
John L. Lovecchio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Drug Resistance ◽  
Statistical Significance ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
In Vitro Assays ◽  
Rank Test ◽  
Assay Sensitivity ◽  
Vitro Assay

e16546 Background: Carboplatin sensitivity in drug resistance assays has been shown to be an independent predictor of longer progression free interval with conflicting results in overall survival. We evaluated in vitro drug resistance for carboplatin and paclitaxel combination and its correlation with progression free survival (PFS) and overall survival (OS). Methods: From April 1, 2006 to December 12, 2011, in vitro drug resistance assays were sent after cytoreductive surgery for primary epithelial ovarian cancer. Patients were analyzed according to drug resistance scoring system of low drug resistance (S), intermediate drug resistance (I), and extreme drug resistance (R). Retrospective chart review was performed to evaluate PFS and OS. The Kaplan Meier product limit method was used to estimate OS and PFS. Survival curves were compared between groups using the log rank test. Results: From a total of 142 patients: 57 were S, 52 I, and 33 R; 77% were responsive (S+I) to carboplatin and paclitaxel combination. At median follow-up of 18 months, PFS and OS rates were 58.1 and 91.3% respectively for S, 66.1 and 78.7% for I, and 43.2% and 84.3% for R. At 36 months, the PFS and OS rates were 52.3 and 61.1% for S, 51.3 and 55.3% for I and 39.3% and 48.7% for R. There was OS advantage between the S and I compared to R. There were no significant differences in PFS curves (p<0.281) or OS curves (p<0.46). Conclusions: Although sensitivity to carboplatin/ paclitaxel resulted in longer OS, the results were not statistically significant. Our cohorts were small and we may not have had the power to capture statistical significance. A larger multicenter analysis would be needed to further evaluate this finding. In addition, one of the regimens our patients received on relapse was bevacizumab which was not evaluated in the in vitro assay sensitivity assay. Bevacizumab has also been included in first line treatment in combination with platinum/ taxane regimen. Future analysis of in vitro assays may need to include biologics.

Clinical performance of a comprehensive novel liquid biopsy test for identifying non-small cell lung cancer (NSCLC) patients for treatment with osimertinib.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9553-9553
Author(s):  
Jhanelle Elaine Gray ◽  
Ji-Youn Han ◽  
Aino Telaranta-Keerie ◽  
Xiangning Huang ◽  
Alexander Kohlmann ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Liquid Biopsy ◽  
Clinical Performance ◽  
Cox Model ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Single Nucleotide Variants ◽  
Biomarker Testing ◽  
Nsclc Patients ◽  
Egfr Tki

9553 Background: Genotyping is required to identify cancer patients (pts) eligible for targeted therapy; however, many do not receive biomarker testing, in part due to limitations associated with tissue-only genotyping practices and the growing list of biomarkers recommended to be tested. Liquid biopsy overcomes many of these limitations but is not yet fully adopted. We report here the clinical performance of a comprehensive liquid biopsy test based on next generation sequencing (NGS) of circulating tumor DNA (ctDNA) for the identification of NSCLC patients with EGFR exon 19 deletions (ex19del) or L858R mutations ( EGFRm) or EGFR T790M, eligible for treatment with osimertinib. Methods: 441 (79%) of 556 pts randomized in FLAURA (NCT02296125; first-line osimertinib vs comparator EGFR TKI in EGFRm NSCLC) and 300 (72%) of 419 pts from AURA3 (NCT012151981; osimertinib vs chemotherapy in NSCLC pts with T790M at progression on EGFR TKI) were retrospectively tested with Guardant360 (G360), a 74-gene ctDNA NGS assay assessing single nucleotide variants, insertion-deletions, amplifications, and fusions in genes relevant to targeted therapy selection as well as microsatellite instability. Progression-free survival (PFS) of pts with EGFRm or T790M detected by G360 was compared to pts detected by the cobas EGFR Mutation Test (cobas) using tissue or plasma with an unadjusted cox model. Results: Treatment with osimertinib was associated with a significant PFS benefit relative to control therapy in NSCLC pts with EGFRm (FLAURA) and T790M (AURA3) detected using G360 (Table). Observed clinical benefit for pts with EGFRm or T790M detected by G360 was similar to that for pts with EGFRm or T790M identified by cobas using tissue or plasma specimens. Conclusions: This analysis demonstrates that G360 accurately identifies pts for osimertinib therapy while simultaneously providing comprehensive genotyping for other therapeutic molecular targets. The application of NGS liquid biopsy has the potential to increase rates of pts genotyped and access to precision medicine. [Table: see text]

scholarly journals Skin Toxicity as Predictor of Survival in Refractory Patients with RAS Wild-Type Metastatic Colorectal Cancer Treated with Cetuximab and Avelumab (CAVE) as Rechallenge Strategy

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5715
Author(s):  
Davide Ciardiello ◽  
Vincenzo Famiglietti ◽  
Stefania Napolitano ◽  
Lucia Esposito ◽  
Nicola Normanno ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multivariate Analysis ◽  
Metastatic Colorectal Cancer ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Progression Free Survival ◽  
Skin Toxicity ◽  
Circulating Tumor Dna ◽  
Wild Type ◽  
Line Of Therapy

The single-arm phase II CAVE mCRC trial evaluated the combination of cetuximab plus avelumab as rechallenge strategy in RAS wild-type (WT) metastatic colorectal cancer (mCRC) patients, with clinical response to first-line anti-EGFR-based chemotherapy, who progressed and received a subsequent line of therapy. The correlation of skin toxicity (ST) and different clinico-molecular variables with overall survival (OS), progression-free survival (PFS) and response rate (RR) was assessed at univariate and multivariate analysis. A total of 33/77 (42.9%) patients experienced grade 2–3 ST and displayed median OS (mOS) of 17.8 months (CI 95%, 14.9–20.6); whereas 44/77 (57.1%) patients with grade 0–1 ST exhibited mOS of 8.2 months (CI 95%, 5.5–10.9), (hazard ratio (HR), 0.51; CI 95%, 0.29–0.89; p = 0.019). Median PFS (mPFS) was 4.6 months (CI 95%, 3.4–5.7) in patients with grade 2–3 ST, compared to patients with grade 0–1 ST with mPFS of 3.4 months (CI 95%, 2.7–4.1; HR, 0.49; CI 95%, 0.3–0.8; p = 0.004). Grade 2–3 ST (HR, 0.51; CI 95%, 0.29–0.89; p = 0.019) and RAS/BRAF/EGFR WT circulating tumor DNA (ctDNA) (HR, 0.50; CI 95%, 0.27–0.9; p = 0.019) had a statistically significant effect on OS at univariate analysis. At the multivariate analysis, RAS/BRAF/EGFR WT ctDNA status maintained statistical significance (HR, 0.49; CI 95%, 0.27–0.9; p = 0.023), whereas there was a trend towards ST grade 2–3 (HR, 0.54; CI 95%, 0.29–1.01; p = 0.054). Skin toxicity is a promising biomarker to identify patients with mCRC that could benefit of anti-EGFR rechallenge.

scholarly journals Higher Caloric Refeeding Is Safe in Hospitalised Adolescent Patients with Restrictive Eating Disorders

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Elizabeth K. Parker ◽  
Sahrish S. Faruquie ◽  
Gail Anderson ◽  
Linette Gomes ◽  
Andrew Kennedy ◽  
...  
Keyword(s):  
Eating Disorders ◽  
Weight Gain ◽  
Statistical Significance ◽  
Caloric Intake ◽  
Tube Feeding ◽  
Retrospective Chart Review ◽  
Refeeding Syndrome ◽  
Restrictive Eating ◽  
Weight Restoration ◽  
The Mean

Introduction. This study examines weight gain and assesses complications associated with refeeding hospitalised adolescents with restrictive eating disorders (EDs) prescribed initial calories above current recommendations.Methods. Patients admitted to an adolescent ED structured “rapid refeeding” program for >48 hours and receiving ≥2400 kcal/day were included in a 3-year retrospective chart review.Results. The mean (SD) age of the 162 adolescents was 16.7 years (0.9), admission % median BMI was 80.1% (10.2), and discharge % median BMI was 93.1% (7.0). The mean (SD) starting caloric intake was 2611.7 kcal/day (261.5) equating to 58.4 kcal/kg (10.2). Most patients (92.6%) were treated with nasogastric tube feeding. The mean (SD) length of stay was 3.6 weeks (1.9), and average weekly weight gain was 2.1 kg (0.8). No patients developed cardiac signs of RFS or delirium; complications included 4% peripheral oedema, 1% hypophosphatemia (<0.75 mmol/L), 7% hypomagnesaemia (<0.70 mmol/L), and 2% hypokalaemia (<3.2 mmol/L). Caloric prescription on admission was associated with developing oedema (95% CI 1.001 to 1.047;p=0.039). No statistical significance was found between electrolytes and calories provided during refeeding.Conclusion. A rapid refeeding protocol with the inclusion of phosphate supplementation can safely achieve rapid weight restoration without increased complications associated with refeeding syndrome.

scholarly journals Circulating tumor DNA dynamics in advanced breast cancer treated with CDK4/6 inhibition and endocrine therapy

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Olga Martínez-Sáez ◽  
Tomás Pascual ◽  
Fara Brasó-Maristany ◽  
Nuria Chic ◽  
Blanca González-Farré ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Endocrine Therapy ◽  
Methodological Approach ◽  
Progression Free Survival ◽  
Circulating Tumor Dna ◽  
Advanced Breast ◽  
Dna Dynamics ◽  
Ca 15.3 ◽  
Tumor Dna

AbstractCirculating tumor DNA (ctDNA) levels may predict response to anticancer drugs, including CDK4/6 inhibitors and endocrine therapy combinations (CDK4/6i+ET); however, critical questions remain unanswered such as which assay or statistical method to use. Here, we obtained paired plasma samples at baseline and week 4 in 45 consecutive patients with advanced breast cancer treated with CDK4/6i+ET. ctDNA was detected in 96% of cases using the 74-gene Guardant360 assay. A variant allele fraction ratio (VAFR) was calculated for each of the 79 detected mutations between both timepoints. Mean of all VAFRs (mVAFR) was computed for each patient. In our dataset, mVAFR was significantly associated with progression-free survival (PFS). Baseline VAF, on-treatment VAF or absolute changes in VAF were not associated with PFS, nor were CA-15.3 levels at baseline, week 4 or the CA-15.3 ratio. These findings demonstrate that ctDNA dynamics using a standardized multi-gene panel and a unique methodological approach predicts treatment outcome. Clinical trials in patients with an unfavorable ctDNA response are needed.

scholarly journals Busulfan plus melphalan versus melphalan alone conditioning regimen after bortezomib based triplet induction chemotherapy for patients with newly diagnosed multiple myeloma

2021 ◽  
Vol 12 ◽  
pp. 204062072110129
Author(s):  
Songyi Park ◽  
Dong-Yeop Shin ◽  
Junshik Hong ◽  
Inho Kim ◽  
Youngil Koh ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Induction Chemotherapy ◽  
Statistical Significance ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cell Engraftment ◽  
The Difference ◽  
High Dose Melphalan

Background: High dose melphalan (HDMEL) is considered the standard conditioning regimen for autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients. Recent studies showed superiority of busulfan plus melphalan (BUMEL) compared to HDMEL as a conditioning regimen. We compared the efficacy of HDMEL and BUMEL in newly diagnosed Asian MM patients, who are often underrepresented. Methods: This is a single-center, retrospective study including MM patients who underwent ASCT after bortezomib-thalidomide-dexamethasone (VTD) triplet induction chemotherapy between January 2015 and August 2019. Result: In the end, 79 patients in the HDMEL group were compared to 31 patients in the BUMEL group. There were no differences between the two groups with regards to sex, age at ASCT, risk group, and stage. The HDMEL group showed better response to pre-transplant VTD compared to BUMEL, but after ASCT the BUMEL group showed better overall response. In terms of progression-free survival (PFS), although BUMEL showed trends towards better PFS regardless of pre-transplant status and age, the difference did not reach statistical significance. The BUMEL group more often experienced mucositis related to chemotherapy, but there was no difference between the two groups with regards to hospitalization days, cell engraftment, and infection rates. Conclusion: BUMEL conditioning deserves attention as the alternative option to HDMEL for newly diagnosed MM patients, even in the era of triplet induction chemotherapy. Specifically, patients achieving very good partial response (VGPR) or better response with triplet induction chemotherapy might benefit the most from BUMEL conditioning. Tailored conditioning regimen, based on patient’s response to induction chemotherapy and co-morbidities, can lead to better treatment outcomes.

scholarly journals Emerging Lab-on-a-Chip Approaches for Liquid Biopsy in Lung Cancer: Status in CTCs and ctDNA Research and Clinical Validation

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2101
Author(s):  
Ângela Carvalho ◽  
Gabriela Ferreira ◽  
Duarte Seixas ◽  
Catarina Guimarães-Teixeira ◽  
Rui Henrique ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Liquid Biopsy ◽  
Residual Disease ◽  
Lab On A Chip ◽  
Microfluidic Devices ◽  
Early Recurrence ◽  
Circulating Tumor Dna ◽  
Clinical Validation ◽  
Liquid Biopsies ◽  
Lung Cancer Patients

Despite the intensive efforts dedicated to cancer diagnosis and treatment, lung cancer (LCa) remains the leading cause of cancer-related mortality, worldwide. The poor survival rate among lung cancer patients commonly results from diagnosis at late-stage, limitations in characterizing tumor heterogeneity and the lack of non-invasive tools for detection of residual disease and early recurrence. Henceforth, research on liquid biopsies has been increasingly devoted to overcoming these major limitations and improving management of LCa patients. Liquid biopsy is an emerging field that has evolved significantly in recent years due its minimally invasive nature and potential to assess various disease biomarkers. Several strategies for characterization of circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) have been developed. With the aim of standardizing diagnostic and follow-up practices, microfluidic devices have been introduced to improve biomarkers isolation efficiency and specificity. Nonetheless, implementation of lab-on-a-chip platforms in clinical practice may face some challenges, considering its recent application to liquid biopsies. In this review, recent advances and strategies for the use of liquid biopsies in LCa management are discussed, focusing on high-throughput microfluidic devices applied for CTCs and ctDNA isolation and detection, current clinical validation studies and potential clinical utility.

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