Cell-free DNA as a surrogate marker in patients with CRPCA undergoing taxane-based chemotherapy.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. e584-e584 ◽  
Author(s):  
Friederike Haidl ◽  
Alexandra Kienel ◽  
David Pfister ◽  
Axel Heidenreich
Keyword(s):  
Lymph Node ◽  
Bone Metastasis ◽  
Lymph Node Metastasis ◽  
Specific Antigen ◽  
Surrogate Marker ◽  
Castration Resistant Prostate Cancer ◽  
Cell Free Dna ◽  
Node Metastasis ◽  
Free Dna ◽  
Median Serum

e584 Background: Taxane-based chemotherapy is one of the first-line life prolonging therapeutic approaches in metastatic castration-resistant prostate cancer (mCRPCA). Until now, there is no valid surrogate marker directly reflecting therapeutic response. Prostate specific antigen (PSA) and imaging studies are used to monitor therapy. The aim of this study was to assess whether circulating cell-free DNA (cfDNA) is suitable as a predictive and prognostic marker. Methods: cfDNA was isolated in 74 patients with mCRPCA receiving taxane based chemotherapy. Median serum cfDNA - concentration was correlated with localization of metastasis and tumor burden (bone, lymph node and visceral). In addition we examined the change of cfDNA - concentration under treatment. The median serum cfDNA - concentration at the time of 1st, 5th and 10th cycle of chemotherapy was correlated with PSA response (>80%, >50%, <30% decrease). Results: We identified 21 patients with a PSA decrease >80%, 41 patients with a PSA decrease >50%, 12 patients with a PSA decrease <30 % and 15 patients with a PSA rise during treatment. Median cfDNA concentration in patients with a PSA decrease of >80% was 34.96 ng/ml, in patients with a PSA decrease > 50% 34.96 ng/ml and in patients with a PSA decrease < 30% 38.475 ng/ml. The Median cfDNA concentration in patients with a PSA rise was 31.25 ng/ml. Median cfDNA concentration in patients with lymph node metastasis was 33.78 ng/ml, with bone metastasis < 3 34.24 ng/ml, bone metastasis >3 31.97 ng/ml and with visceral metastasis 34.57 ng/ml. There was no significant correlation between median cfDNA - concentration and type of metastasis (cfDNA vs. PSA bone metastasis <3, P = 0,56938, cfDNA vs. PSA bone metastasis >3 P = 0.472, cfDNA vs. PSA lymph node metastasis P = 0.423). There was no significant change of median cfDNA concentration under treatment ( P > 0.05). Conclusions: Although cfDNA-concentration is a prognostic and predictive marker for survival and therapy response as shown recently, our findings suggest that cfDNA as a surrogate marker is unsuitable.

Droplet digital polymerase chain reaction for detection and quantification of cell-free DNA TP53 target somatic mutations in oral cancer

2021 ◽  
pp. 1-13
Author(s):  
Li-Han Lin ◽  
Hui-Wen Cheng ◽  
Chung-Ji Liu
Keyword(s):  
Polymerase Chain Reaction ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Primary Tumor ◽  
Somatic Mutations ◽  
Chain Reaction ◽  
Node Metastasis ◽  
Free Dna ◽  
Polymerase Chain ◽  
Digital Polymerase Chain Reaction

BACKGROUND: TP53 mutation is a driver mutation of oral carcinogenesis. This study investigated cancerous and cell-free DNA (cfDNA) in patients with oral squamous cell carcinoma (OSCC) to detect the target hotspot somatic mutation of TP53. OBJECTIVE: TP53 target hotspot mutations were determined in surgically resected primary tumor samples from 107 OSCC patients. METHODS: Cancerous and cfDNA samples were examined for mutations through droplet digital polymerase chain reaction (ddPCR) by using mutation-specific assays. The ddPCR results were evaluated alongside clinicopathological data. RESULTS: In total, 23 cases had target TP53 mutations in varying degrees. We found that OSCC had relatively low cfDNA shedding, and mutations were at low allele frequencies. Of these 23 cases, 13 had target TP53 mutations in their corresponding cfDNA. Target somatic mutations in cancerous DNA and cfDNA are related to cervical lymph node metastasis. The cfDNA concentration is related to primary tumor size, lymph node metastasis, and OSCC stage. CONCLUSIONS: Our results show that the detection of TP53 target somatic mutations in OSCC patients by using ddPCR is technically feasible. Low levels of cfDNA may produce different results between cancerous tissue and cfDNA analyses. Future research on cfDNA may quantify diagnostic biomarkers in the surveillance of OSCC patients.

scholarly journals MON-530 Local Lymph Node Metastasis Is Less Common in RAS- Mutated Thyroid Cancer Compared to BRAFV600E- Mutated Thyroid Cancer

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Mayumi Endo ◽  
Fadi Nabhan ◽  
Pamela Brock ◽  
Katie Roll ◽  
Jennifer Anne Sipos ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Lymph Node ◽  
Bone Metastasis ◽  
Lymph Node Metastasis ◽  
Papillary Thyroid Cancer ◽  
Papillary Thyroid ◽  
Brafv600e Mutation ◽  
Ras Mutation ◽  
Node Metastasis ◽  
Local Lymph Node

Abstract Introduction: Somatic mutations of RAS- and BRAFV600E- are the most common driver mutation in thyroid cancer (TC) and in the majority of cases, these are mutually exclusive1,2. Clinical characteristics of TC with either RAS or BRAFV600E mutation is not systemically studied. Methods: This is a retrospective study at the Ohio State University (OSU) from 1/2000 to 12/2018. Data were extracted from OSU Endocrine Neoplasia Repository (ENR). Medullary thyroid cancer was excluded. The treating physician determined patient management. Statistical analysis was performed with the chi-square test for categorical values and Mann-Whitney U test for continuous unpaired values. Two-sided P values of less than 0.05 were considered statistically significant. Results: Out of 320 patients, 152 patients had a positive mutational profile. Of these, 128 patients had a BRAFV600E mutation and 14 had a RAS mutation. Details of RAS mutation were as follows; NRASQ61K (n=2), NRASQ61R (n=1), HRASQ61R (n=1), HRASQ61K (n=1), NRAS without further details (n=9). Local lymph node metastasis was significantly less in RAS mutated cancer (58% vs 16%, p&lt;0.05). Lymph node metastasis was limited to N1a in all RAS group, whereas 38% of BRAFV600E had N1b status. The number of positive lymph nodes were significantly fewer in the RAS group (mean 0.42 vs. 9.1, p=0.003). None of the patients in RAS group developed subsequent local neck recurrence, whereas 19% of BRAFV600E group developed a recurrence (p=0.05). Bone metastasis was more common in RAS compared to BRAFV600E group (21% vs 6%, p=0.04) but there were no differences in other distant metastases. Presence of extrathyroidal extension was significantly higher in BRAFV600E compared to RAS group (58 % vs 8%; p=0.04). Classic variant papillary thyroid cancer was the most common histologic diagnosis with both mutations, however, follicular-variant papillary thyroid cancer was more common in RAS than BRAFV600E group (29% vs 8%, p=0.04) and follicular thyroid cancer was only seen in the RAS group (25% vs 0%, p&lt;0.05). There was no difference in gender, age at diagnosis, disease status after initial therapy, RAI treatment, RAI dosage, and mortality between the groups. Conclusion: Thyroid cancer associated with a RAS-mutation has less tendency to metastasize locally and has a higher incidence of bone metastasis compared to thyroid cancer with BRAFV600E-mutation. Individualized clinical follow up may be indicated depends on their mutational profile. References: 1. Cancer Genome Atlas Research N. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676-690. 2. Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318-2326.

Lymph node metastasis to predict overall survival in oligometastatic prostate cancer in Asian patients.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 237-237
Author(s):  
Junryo Rii ◽  
Shinichi Sakamoto ◽  
Yasutaka Yamada ◽  
Yusuke Imamura ◽  
Kazuyoshi Nakamura ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Lymph Node ◽  
Bone Metastasis ◽  
Lymph Node Metastasis ◽  
Bone Metastases ◽  
Locally Advanced ◽  
Local Treatment ◽  
Node Metastasis ◽  
Oligometastatic Prostate Cancer ◽  
Wide Range

237 Background: The oligometastatic cancer has been suggested as an intermediate state between localized disease and wide range metastases. Clinical significance of local treatment in oligometastatic prostate cancer (PCa) has been a recent topic. However, due to racial differences, there are no standard definitions of oligometastasis, especially in Asians. Here we studied the risk factor among Japanese oligometastatic PCa patients. Methods: We retrospectively analyzed the medical record of 207 patients, including locally advanced (T3 or T4N0M0), lymph-node-positive (N1), and ≤10 bone metastases cancer. All patients received androgen deprivation therapy only. The number of bone metastasis and clinical factors were evaluated in association with OS. Results: Median age, PSA at baseline and OS were 73 years, 48.8ng/ml and 121 months respectively. The cutoff value for the number of bone metastases that have the greatest impact on OS was ≥2 (HR 3.05, p = 0.0001), followed by ≥7 (HR 3.03, p = 0.0005). In multivariate analysis, lymph node metastasis (HR 2.54, p = 0.003) and ≥2 bone metastases (HR 2.67, p = 0.009) were independent predictors of OS. In risk classification based on independent predictors, OS was significantly classified in High (3-4 factors), Intermediate (1-2 factors), and Low (no factor) risk groups (p <0.0001). Furthermore, even among same risk factors group, inclusion of lymph node metastasis significantly increased the HR by 2.34 (p = 0.039). Conclusions: Not only the number of bone metastasis but also lymph node metastasis predict OS of oligometastatic PCa patients.[Table: see text]

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