Association of telomere length with clinical outcomes in patients with colorectal carcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14540-e14540
Author(s):  
Mahadi Ali Baig ◽  
Titto A Augustine ◽  
Amartej Merla ◽  
Gil Atzmon ◽  
Temuri Budagov ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Copy Number ◽  
Tandem Repeats ◽  
Progression Free Survival ◽  
Housekeeping Gene ◽  
Tissue Samples ◽  
Paired Samples ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Metastatic Sites

e14540 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem”. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 118 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (>/< median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Stage at diagnosis (localized Vs Metastatic) had a statistically significant difference in TL (mean BP 4047 vs. 5704; p=0.03). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs 5295 p=0.022). Patients treated with cetuximab/panitumumab who had Shorter TL were also found to have significantly decreased Overall Survival (OS) (101.1 Months vs 153.02 Months p<0.0001). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. There was no difference of TL seen with size of the tumor. Furthermore there was no difference in TL between various metastatic sites. Conclusions: TL is a potential biomarker predictive of clinical outcome (OS & PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.

Association of telomere length (TL) with clinical outcomes in patients with colorectal carcinoma (CRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 418-418
Author(s):  
Mahadi Ali Baig ◽  
Amartej Merla ◽  
Titto A Augustine ◽  
Gil Atzmon ◽  
Temuri Budagov ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Copy Number ◽  
Tandem Repeats ◽  
Progression Free Survival ◽  
Housekeeping Gene ◽  
Tissue Samples ◽  
Paired Samples ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Metastatic Sites

418 Background: Telomeres (T) consist of thousands of copies of TTAGGG tandem repeats capping the ends of the chromosome. T along with enzyme telomerase provides protection against any threats to the genome that might arise as a consequence of “end replication problem.” During aberrant cell proliferations the normal check points of cell cycle is compromised leading to unrestricted cell division with extremely short T and subsequent genomic instability. Studies have linked short TL with premalignant and malignant stages of CRC carcinogenesis. However, the relation of TL to the clinical outcomes has not been conclusively determined. In this study we evaluated the association of TL with clinical outcomes in a cohort of 75 CRC patients. Methods: Tumor DNA was isolated from formalin fixed paraffin embedded specimens. TL was measured by using a qRT-PCR method that provided the relative T copy number, compared to reference copy number of the housekeeping gene, β-Globin, which resulted in a T/S ratio. One T/S ratio unit is equivalent to a mean TL of 4,270 base pairs (BP). Results: From 75 patients, 122 tissue samples were identified (66 primary, 52 metastases, 29 matched pairs). Age at diagnosis (>/< median) had a statistically significant difference in TL (mean BP 4700 vs. 4374; p=0.05) with shorter TL in the advanced age. Females had longer TL compared to men (mean BP 4722 vs. 3669 respectively; p=0.04). Shorter TL was associated with shorter progression free survival (PFS) for patients treated with cetuximab/panitumumab (3963 vs. 5295 p=0.04). There was a trend towards increased overall survival (>/< median) with longer TL (4934 vs. 4117; p=0.08). We failed to find a difference in the TL between primary and metastatic sites in the 29 patients with paired samples. Conclusions: TL is a potential biomarker predictive of clinical outcome (PFS) for patients treated with cetuximab/panitumumab. Tumor TL reduces with advancing age and appears to be sex dependent. Further studies to validate TL’s predictive role in patient outcomes are underway.

Association of basophil to lymphocyte ratio (BLR) with clinical outcomes in metastatic hormone sensitive prostate cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e17049-e17049
Author(s):  
Katherine Emilie Rhoades Smith ◽  
Limeng Wan ◽  
Yuan Liu ◽  
Jacqueline T Brown ◽  
Greta Russler ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Outcomes ◽  
Laboratory Data ◽  
Progression Free Survival ◽  
Continuous Variable ◽  
Cancer Center ◽  
Lymphocyte Ratio ◽  
Potential Biomarker ◽  
Significant Difference ◽  
Hormone Sensitive

e17049 Background: There is limited biomarker data available for metastatic hormone sensitive prostate cancer (mHSPC). Inflammatory markers found on routine clinical lab data, including leukocyte to lymphocyte ratios calculated from complete blood counts (CBC), is associated with clinical outcomes (CO) in different malignancies. We investigated the association between basophil-to-lymphocyte ratio (BLR) and CO in a racially diverse patient population with mHSPC. Methods: We performed a retrospective multicenter review from Winship Cancer Institute at Emory University and Georgia Cancer Center for Excellence at Grady Memorial Hospital (2014 – 2020). Demographics, disease characteristics, and laboratory data were collected at the start of upfront therapy with either docetaxel (DOC) or abiraterone (ABI). Overall survival (OS) and progression-free survival (PFS) were used to measure CO. Results: Included were 165 patients with mHSPC with a median follow-up time of 22.6 months. 89 (53.9%) were Black and 76 (46.1%) were Non-Black (White, Asian, or Hispanic). 106 (63%) had Gleason scores of 8-10 and 105 (63.6%) were classified as high-volume disease (per CHAARTED trial criteria). 92 (55.8%) received DOC and 73 (44.2%) received ABI. Worse CO were associated with high BLR at an optimal cut of 0.0265 (range 0 – 0.81 , mean of 0.03, standard deviation 0.09). Elevated BLR is associated with decreased OS (HR 3.51, 1.79 – 6.91, p <0.001) and PFS (HR 1.85, 1.14 – 3.00, p 0.013) in multivariable analyses (MVA). High BLR and low BLR groups were similar except for age as a continuous variable, which was associated with high BLR. Otherwise, there were no significant difference for all reported clinical characteristics, including drug (DOC vs ABI), race (Black vs Non-Black), Gleason, disease volume (per CHARRTED criteria), ECOG, or BMI. Conclusions: In mHSPC, high baseline BLR is associated with worse OS and PFS. Our results are the first to identify that BLR is associated with CO in mHSPC. Further study is needed to validate BLR as a potential biomarker.[Table: see text]

Early circulating tumor (ct) DNA dynamics and efficacy of lorlatinib: Analysis from the CROWN study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9011-9011
Author(s):  
Ross A. Soo ◽  
Jean-Francois Martini ◽  
Anthonie J. van der Wekken ◽  
Shunsuke Teraoka ◽  
Alice T. Shaw ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Kinase Inhibitor ◽  
Progression Free Survival ◽  
Molecular Response ◽  
Similar Response ◽  
Dna Dynamics ◽  
Paired Samples ◽  
Biomarker Analysis ◽  
Alk Positive ◽  
Ctdna Analysis

9011 Background: Lorlatinib, a third-generation ALK tyrosine kinase inhibitor, significantly improved progression-free survival (PFS) and overall/intracranial responses vs crizotinib in patients (pts) with previously untreated ALK-positive advanced non-small cell lung cancer (NSCLC) in the ongoing randomized Phase 3 CROWN study (NCT03052608). To identify whether additional molecular biomarker analysis correlated with efficacy, we evaluated early ctDNA dynamics compared with clinical outcomes. Methods: Plasma samples were prospectively collected at screening (SC), week 4 (cycle 2, day 1 [C2D1]), week 24 (C7D1), and end of treatment for ctDNA analysis. ctDNA was analyzed using Guardant360CDx (Guardant Health, Inc., Redwood City, CA, USA). Mean variant allele fraction (VAF) of ALK alterations (fusions and/or mutations) and overall detected alterations at each time point and longitudinal mean change (dVAF) as (VAFC2D1) – (VAFSC) were calculated; dVAF <0 indicated decreased ctDNA at week 4. Objective tumor response and PFS were evaluated according to dVAF. These analyses were repeated vs ctDNA results at week 24. Additional correlation analyses between depth of molecular response and/or ctDNA clearance and clinical outcomes are ongoing. Results: Paired samples were available at SC and week 4 from 232 of 255 pts included in the ctDNA analysis: 118/130 (90.8%) in the lorlatinib arm and 114/125 (91.2%) in the crizotinib arm. ALK alterations were detected in 122/232 (52.6%) pts at SC (62/118 [52.5%] from the lorlatinib arm) but only 19/232 (8.2%) at week 4 (8/118 [6.8%] from the lorlatinib arm). Mean VAF of ALK alterations at week 4 was significantly decreased compared with SC in both treatment arms (lorlatinib -1.54, crizotinib -1.25; both P<0.0001; P=0.4239 between arms). In the lorlatinib arm, mean VAF at week 4 was significantly decreased compared with SC in pts with a complete or partial response (dVAF -1.53; n=47; P<0.0001), or stable disease (dVAF -1.37; n=12; P=0.0304). Similar results were observed in the crizotinib arm. In pts with dVAF <0 for ALK alterations, mean percent change from screening in tumor size was -40.8% with lorlatinib (n=59) and -38.7% with crizotinib (n=58). Only 2 pts had dVAF ≥0, both from the crizotinib arm. Median PFS for pts with dVAF <0 for ALK alterations was not reached in the lorlatinib arm (n=62), and was 7.4 months (95% CI, 7.2–9.3) in the crizotinib arm (n=58). Similar response and PFS data were observed in the analysis of dVAF for ALK alterations at week 24. Conclusions: Early ctDNA dynamics may predict lorlatinib efficacy in pts with previously untreated ALK-positive NSCLC. The magnitude of reduction in ctDNA at 4 weeks may be associated with better responses and potentially longer PFS. These findings further support the utility of dynamic ctDNA monitoring in ALK-positive NSCLC. Reference: Shaw AT, et al. N Engl J Med. 2020;383:2018-2029. Clinical trial information: NCT03052608.

282 CERVICAL ESOPHAGECTOMY USING “LARYNX ROTATION METHOD” CAN OBTAIN GOOD CLINICAL OUTCOMES.

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
Y Nakajima ◽  
K Ogiya ◽  
H Endo ◽  
T Okada ◽  
A Hoshino ◽  
...  
Keyword(s):  
Survival Rate ◽  
Clinical Outcomes ◽  
Primary Tumor ◽  
Progression Free Survival ◽  
Therapeutic Modality ◽  
Laryngeal Function ◽  
Larynx Preservation ◽  
Rotation Method ◽  
Significant Difference ◽  
Cervical Esophagectomy

Abstract   In the treatment of cervical esophageal carcinoma (CEC), preservation of laryngeal function is required as well as curability. Therefore, chemoradiotherapy (CRT) is often selected for larynx-preservation. In our department, larynx-preserving surgery using “larynx-rotation method” is aggressively carried out even when the oral side of the tumor margin extends beyond the esophageal orifice. In this study, we analyzed the clinical outcomes of the resectable CEC and examined ``Which therapeutic modality should be selected, surgery or CRT?'' Methods In the present study, 40 patients whose primary tumor was resectable Stage II/III CEC treated in our department since 2008, whose advanced primary tumor lesion was limited within cervical esophagus, and who undergo surgery or curative CRT were enrolled. The clinical outcomes were retrospectively analyzed. Results The Op group included 25 patients. All of the Op group patients could preserve the larynx. In the CRT group, 2 patients were performed pharyngo-laryngo-cervical esophagectomy as the salvage surgery. 1- and 3-year progression-free survival rate was 80.1 and 69.3% in the Op group, and 63.0 and 31.5% in the CRT group. 1-, 3- and 5-year overall survival rate was 95.8, 80.9 and 67.4% in the Op group and 78.6, 64.3 and 46.9% in the CRT group, respectively. Although there was no significant difference, the Op group showed relatively better clinical outcomes. Conclusion Cervical esophagectomy using “larynx-rotation method” could obtain good therapeutic outcomes while preserving the larynx. Especially in case cervical esophagectomy is sufficient as the curative resection, because the surgical invasion is little and the postoperative quality of life is good while preserving the larynx and the whole stomach, surgery is considered useful treatment modality.

Association between single nucleotide polymorphisms (SNPs) of genes involved in spindle assembly checkpoint (SAC) and clinical outcomes in advanced gastric cancer (AGC) patients (pts) treated with taxane-based chemotherapy.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 79-79
Author(s):  
Shinichi Yamauchi ◽  
Satoshi Okazaki ◽  
Afsaneh Barzi ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Spindle Assembly Checkpoint ◽  
Direct Sequencing ◽  
Univariate Analysis ◽  
Nucleotide Polymorphisms ◽  
Tissue Samples ◽  
Significant Difference ◽  
Validation Set ◽  
The Impact

79 Background: Taxanes which disrupt the microtubule function and inhibit the process of cell division have shown encouraging activity in the treatment of AGC. Resistance to these agents often becomes a problem in clinical settings and its mechanism hasn’t been dissolved conclusively. SAC is a safety device ensures the proper chromosome segregation in mitosis and is required for taxane-induced cell death. We hypothesized genetic variants in SAC genes may be associated with clinical outcomes in pts with AGC treated with taxane. Methods: Genomic DNA was isolated from blood or tissue samples of 39 U.S. pts (median age 57; median follow-up 6.4 months) for evaluation set and 39 Japanese (JPN) pts (median age 63; median follow-up 9.4 months) for validation set, with AGC treated with taxane. Twenty-five functionally significant SNPs in SAC genes (MAD1, MAD2, BUB3, BUBR1, RAN, TPX2, CDC20, AURKA, AURKB, RCC1, ANAPC10, ANAPC13) were analyzed by PCR-based direct sequencing and evaluated for association with outcomes. Results: In univariate analysis, rs4236271 (MAD1), rs6954673 (MAD1), and rs2064863 (AURKA) showed a significant difference in 6-month (mo) progression-free survival (PFS) rate [(C/C 42%, C/T 12%; HR 2.66, P=0.008), (C/C 75%, C/T or T/T 24%; HR 5.10, P=0.008), and (T/T 50%, T/G 15%, G/G 57%; HR1.55, P=0.046), respectively] and 18-mo overall survival (OS) rate [(C/C 40%, C/T 8%; HR3.69, P<0.001), (C/C 56%, C/T or T/T 19%; HR3.60, P=0.004), and (T/T 59%, T/G 15%, G/G 29%; HR 2.02, P=0.047), respectively] in evaluation set. In multivariate analysis, rs4236271 and rs6954673 remained significant in PFS (HR 7.24, P=0.005, HR 14.49, P=0.015, respectively) and OS (HR 7.39, P=0.001, HR 6.37, P=0.002, respectively). In validation set, rs6954763 showed a significant difference in 18-mo OS rate (C/C 16%, C/T or T/T 47%, HR 3.55, P=0.014), but the impact of C/C genotype on OS in the JPN pts was the opposite to the U.S. pts. Conclusions: These results suggest that MAD1 polymorphisms may serve as a prognostic marker in pts with AGC. Further studies using larger population are needed to corroborate our results.

Clinical outcomes of NSCLC patients with acquired RET rearrangement after resistance to osimertinib.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20626-e20626
Author(s):  
Chang Lu ◽  
Jia-Tao Cheng ◽  
Jin Kang ◽  
Yi-Hui Yao ◽  
Xiang-Meng Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Outcomes ◽  
Acquired Resistance ◽  
Progression Free Survival ◽  
Best Supportive Care ◽  
Line Treatment ◽  
Significant Difference ◽  
Ret Rearrangement ◽  
Egfr Mutant

e20626 Background: Resistance mechanisms to osimertinib have raised growing concerns, but those with acquired RET rearrangement is poorly characterized. Methods: We retrospectively identified advanced, EGFR-mutant NSCLC (non-small-cell lung cancer) patients treated with osimertinib between April 9th, 2015 and November 1st, 2018 at our institute. Clinicopathologic features and clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). Overall survival (OS) since 1st line treatment was calculated from first-line treatment start to death or last follow up, and OS post-progression was calculated from osimertinib progression. Median follow-up time was 43.4 months. Results: In the 192 patients treated with osimertinib, 57 had follow-up NGS information after progression, and six harboured acquired RET rearrangement (11%, 6/57). For patients with RET rearrangements when progressed on osimertinib, OS since 1st line treatment (22.9m vs 59.5m, P = 0.021) and OS post-progression (2.1m vs 10.0m, P = 0.031) were significantly shorter compared with non- RET-rearranged cases, whereas no significant difference was found in demographics at the initial lung cancer diagnosis or progression-free survival (PFS) of osimertinib (12.1m vs 5.8m, P = 0.34). Among these six patients, one received best supportive care, two continued to use drugs targeting EGFR but deteriorating soon, three patients tried osimertinib combined with cabozantinib with one benefit from this combination approach. Conclusions: RET rearrangements could exist in EGFR-mutant NSCLC with acquired resistance to osimertinib and linked to inferior survival. Study on the molecular evolution and heterogeneity during treatment course are warranted for further therapeutic strategies. [Table: see text]

scholarly journals Carboxypeptidase N1 is anticipated to be a synergy metrics for chemotherapy effectiveness and prognostic significance in invasive breast cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ranliang Cui ◽  
Chaomin Wang ◽  
Tiantian Li ◽  
Jialei Hua ◽  
Ting Zhao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Progression Free Survival ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Cox Regression Analysis ◽  
Potential Biomarker ◽  
Incidence And Mortality

Abstract Background The incidence and mortality of invasive breast cancer (IBC) are increasing annually. Hence, it is urgently needed to determine reliable biomarkers for not only monitoring curative effects, but evaluating prognosis. In present study, we aim to determine the potential role of Carboxypeptidase N1 (CPN1) in IBC tissues on chemotherapeutic efficacy and poor prognosis. Methods The expression level of CPN1 in IBC tissue samples (n = 123) was quantified by tissue microarray technique and immunohistochemical staining. Moreover, sera of IBC patients (n = 34) that underwent three to five consecutive chemotherapy sessions were collected. The patients were randomly stratified into a training (n = 15) as well as a validation group (n = 19). The expression of serum CA153 and CPN1 was quantified by electrochemiluminescence and ELISA assay, respectively. Results By univariate and multivariate Cox regression analysis, we show that CPN1 expression in IBC tissues, as an independent risk factor, is related to a poor overall survival (OS) and progression-free survival (PFS) (P < 0.05). Analysis of the data revealed that CPN1 over-expression could be consistently linked to adverse clinicopathological features such as lymph node metastasis and the pathological stage (pTNM) (P < 0.05). The serum CPN1 level trajectory of individual patients generally decreased during chemotherapy. In line with these findings were changes in the follow-up ultrasonography and a consistent decrease in serum CPN1 levels. The comparison of the area under the receiver operating curves (ROC) revealed that CPN1 has a better surveillance value than CA153 in the training (AUCCPN1 = 0.834 vs. AUCCA153 = 0.724) as well as the validation set (AUCCPN1 = 0.860 vs. AUCCA153 = 0.720) when comparing cycle2 versus cycle3. Conclusions CPN1 is a suitable potential biomarker for chemotherapeutic surveillance purposes as well as being an appropriate prognostic indicator which would support an improved chemotherapy regimen.

Baseline neutrophil-to-eosinophil ratio (NER) and its association with clinical outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with immune checkpoint inhibitors (CPI).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16569-e16569
Author(s):  
Deepak Ravindranathan ◽  
Yuan Liu ◽  
Dylan J. Martini ◽  
Jacqueline T Brown ◽  
Bassel Nazha ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Clinical Benefit ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
P Value ◽  
Proportional Hazard ◽  
Free Survival ◽  
Cox Proportional Hazard ◽  
Significant Difference

e16569 Background: Inflammatory markers have been studied as prognostic markers in patients with mRCC treated with CPIs. Recently, eosinophilia has been found to be associated with improved survival of patients with melanoma treated with CPIs. We reported baseline NER in patients with mRCC treated with CPIs and its association with clinical outcomes. Methods: We conducted a retrospective analysis of patients with mRCC treated with CPIs at Winship Cancer Institute from 2015-2018. Clinical outcomes were measured as overall survival (OS), progression-free survival (PFS), and clinical benefit (CB). OS and PFS were calculated from CPI-initiation to date of death and radiographic or clinical progression, respectively. Patients with baseline NER were categorized into high or low; high defined as NER > 49.2 and low defined as NER < 49.2. Univariate (UVA) and multivariate (MVA) analyses were carried out for OS and PFS using Cox proportional hazard model. Results: A total of 184 patients were studied with a median follow up of 25.4 months. Median age was 63 years old with 72% male and 20% black. About 25% were in high NER group. The high NER patients had significantly shorter OS in both UVA (HR: 0.58, p-value=0.017) and MVA (HR: 0.62, p-value=0.046) (Table). There was no significant difference between groups for PFS. Clinical benefit was seen in 47.3% of patients with low baseline NER and 40% with high NER. Conclusions: High baseline NER was associated with worse OS in patients with mRCC treated with CPIs. Larger, prospective studies are warranted to validate this hypothesis generating data.[Table: see text]

Illustration of temporal evolution in patients with metastatic renal cell carcinoma (mRCC) using both circulating tumor DNA (ctDNA) and tissue-based genomic data.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 347-347
Author(s):  
Zeynep Busra Zengin ◽  
Caroline Weipert ◽  
Joann Hsu ◽  
Nicholas Salgia ◽  
Chuck Hensel ◽  
...  
Keyword(s):  
Circulating Tumor Dna ◽  
Genomic Profiling ◽  
Temporal Separation ◽  
Tissue Samples ◽  
Sequencing Platform ◽  
Targeted Next Generation Sequencing ◽  
Paired Samples ◽  
Significant Difference ◽  
The Difference ◽  
Ctdna Analysis

347 Background: We have previously demonstrated the feasibility of ctDNA assessment in mRCC and preliminarily showed agreement between ctDNA and tissue-based genomic findings (Zengin et al ESMO 2020). Our data suggested that the degree of agreement is dependent upon the temporal separation of blood and tissue samples. We sought to further explore this temporal impact in a separate validation cohort. Methods: Patients (pts) with mRCC who underwent ctDNA genomic profiling were identified. ctDNA analysis was performed using a CLIA-certified 73-74 gene panel (Guardant360). From this cohort we identified a subset of pts who also underwent tissue-based genomic profiling using either a whole exome sequencing platform (GemExtra [TGen, Phoenix, AZ]) or a targeted next generation sequencing platform (Foundation Medicine [Cambridge, MA] or Tempus [Chicago, IL]). Only alterations covered by both assays were included for the current analysis. The difference in the proportion of alterations detected on tissue and ctDNA was compared between these cohorts and at a 6-mo landmark using the χ2 test. Results: In total, ctDNA and tissue based genomic profiling was assessed in 112 pts (M:F, 81:31); with most common histology was clear cell (85.7%). Median time between ctDNA and tissue assessments was 9.8 months (IQR 1.15-23.7). When examining paired samples in which >1 ctDNA alteration was detected, 32% (43/133) of alterations detected on tissue were also detected in ctDNA. This proportion increased to 43% (29/67) when samples collected within 6 months of each other, and was 51% (28/55) in samples collected within 3 months of each other. There was no significant difference in the frequency of shared mutations between the cohorts (P=0.09; Table). Conclusions: Our study confirms that ctDNA and tissue-based genomic profiling continue to provide consistently high levels of agreement. Notably, the percentage of samples with ≥1 ctDNA alteration detected was significantly lower in both cohorts compared to previous studies in RCC. More shared alterations were found on ctDNA when both ctDNA and tissue-based assessment were obtained at closer intervals. [Table: see text]

scholarly journals PPP1R12A Copy Number Is Associated with Clinical Outcomes of Stage III CRC Receiving Oxaliplatin-Based Chemotherapy

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Chenbo Zhang ◽  
Ajian Li ◽  
Huaguang Li ◽  
Kangsheng Peng ◽  
Qing Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Outcomes ◽  
Copy Number ◽  
Gene Copy Number ◽  
Tumor Location ◽  
Stage Iii ◽  
Gene Copy ◽  
Tissue Samples ◽  
Relative Copy Number ◽  
Colorectal Cancer Patients

Aim. To investigate the correlation between PPP1R12A gene copy number and clinical outcomes of oxaliplatin-based regimen in stage III colorectal cancer (CRC).Methods. A total of 139 paraffin-embedded tissue samples of stage III CRC patients who received oxaliplatin-based treatment after radical surgery were recruited. Genomic DNA was extracted and purified from paraffin-embedded sections. Quantitative PCR methods were used to detect the relative copy number (RCN) of PPP1R12A.Results. Statistical analysis demonstrated that low PPP1R12A RCN was associated with poor RFS (HR=2.186, 95% CI: 1.293–3.696;P=0.003) and OS (HR=2.782, 95% CI: 1.531–5.052;P<0.001). Additionally, when patients were stratified according to subgroups of stage III and tumor location, poor RFS and OS were also observed in the low PPP1R12A RCN group with significance (RFS: IIIBHR=2.870,P<0.001; colonHR=1.910,P=0.037; OS: IIIBHR=3.527,P<0.001; IIICHR=2.662,P=0.049; rectumHR=4.229,P=0.002).Conclusion. Our findings suggest the copy number of PPP1R12A can independently predict recurrence and overall survival of stage III colorectal cancer patients receiving oxaliplatin-based chemotherapy.

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