Exploring fingerprint ctDNA as a stratifying factor in colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16101-e16101
Author(s):  
Wending Sun ◽  
Jianwei Zhang ◽  
Jinwang Wei ◽  
Chun Dai ◽  
Jun Liu ◽  
...  

e16101 Background: Colorectal cancer (CRC) ranks near the top in tumor-related deaths. Its standard-of-care is surgical resection plus adjuvant chemotherapy, which can extend patient’s live and disease-free survival for up to several years. However, choosing an appropriate chemotherapy agent is difficult because CRC is a heterogenous disease. It is believed that molecular stratification can help to improve treatment accuracy and this has been proven by the consensus molecular subtypes (CMS) classification. However, the CMS classification relies on expensive and complex gene-expression profiling, and more cumbersomely, is limited to early stage patients without prior chemotherapy, radiation and metastasis. This situation denies many CRC patients from the benefit of CMS classification. Circulating tumor DNA (ctDNA) is a minimally invasive way to monitor disease progression and treatment response in solid tumors but its clinical utility in CRC remains to be validated. We explore the potential of using patient’s fingerprint ctDNA (defined below) as a stratifying factor in CRC patients to assist clinical decision. Methods: WES is performed on tumor and matched blood samples from 149 CRC patients. Based on the WES result, 20-30 tumor specific genes are selected for each patient and form their ctDNA fingerprints. The patients are grouped according to their level of fingerprint ctDNA (high- vs. low-ctDNA). Results: The two groups of patients show significant difference in treatment responses and mutational profiles. The low-ctDNA group in general respond to treatment well and have good prognosis. The high-ctDNA group, in contrast, often experience relapse or recurrence. Interestingly, the low-ctDNA group is dominated by point and small indel mutations in the top mutated genes while the high-ctDNA group is dominated by gene copy variations (CNV). SMAD4 deficit and DCC amplification are well known CNV in CRC, but they only appear in the high-ctDNA group. Similarly, CNV of AGO2, ACTG1, MYC, and BRD3 are only associated with the high-ctDNA group but not the low-ctDNA group. Conclusions: Our result indicates a strong correlation of fingerprint ctDNA level to both tumor mutational profile and prognosis. This suggests fingerprint ctDNA level may be used as an effective stratifying factor in CRC. At the same time, possibly a common molecular cause is driving persistent ctDNA production in CRC patients, including a large portion of them who have received surgical and adjuvant chemotherapy. Further perspective study, however, is needed to test whether fingerprint ctDNA can be a predictive biomarker.

2003 ◽  
Vol 13 (4) ◽  
pp. 395-404 ◽  
Author(s):  
B. Winter-Roach ◽  
L. Hooper ◽  
H. Kitchener

A systematic review and meta analysis has been undertaken in order to evaluate the effectiveness of adjuvant therapy following surgery for early ovarian cancer. Trials reported since 1990 have been of a higher quality enabling a meta analysis of adjuvant chemotherapy vs adjuvant radiotherapy and a meta analysis of adjuvant chemotherapy vs observation. There was no significant difference between radiotherapy and chemotherapy, though these comprised studies which demonstrated considerable heterogeneity. Chemotherapy did confer significant benefit over observation in terms of both overall and disease free survival. Except for women in whom adequate surgical staging has revealed well differentiated disease confined to one or both ovaries with intact capsule, platinum chemotherapy should be offered to reduce risk of recurrence.


2019 ◽  
Vol 49 (8) ◽  
pp. 714-718
Author(s):  
Hao Yu ◽  
Linlin Zhang ◽  
Dapeng Li ◽  
Naifu Liu ◽  
Yueju Yin ◽  
...  

Abstract Objectives The current study was aimed to evaluate the efficacy and toxicity of postoperative adjuvant chemotherapy (CT) combined with intracavitary brachytherapy (ICRT) in cervical cancer patients with intermediate-risk. Methods We analyzed the medical records of 558 patients who were submitted to radical surgery for Stage IB-IIA cervical cancer. A total of 172 of those 558 patients were considered intermediate-risk according to the GOG criteria. Among those 172 patients, 102 were subjected to CT combined with ICRT (CT+ICRT) and the remaining 70 patients were treated with concurrent chemoradiation (CCRT). The 3-year disease free survival (DFS), overall survival (OS), and complications of each group were evaluated and analyzed. Results No significant difference was observed in 3-year DFS or OS of the patients submitted to CT+ICRT and CCRT. Importantly, the frequencies of grade III to IV acute complications were significantly higher in patients submitted to CCRT than in those treated with CT+ICRT (Hematologic, P = 0.016; Gastrointestinal, P = 0.041; Genitourinary, P = 0.019). Moreover, the frequencies of grade III–IV late complications in patients treated with CCRT were significantly higher compared with CT+ICRT-treated patients (Gastrointestinal, P = 0.026; Genitourinary, P = 0.026; Lower extremity edema, P = 0.008). Conclusions Postoperative adjuvant CT+ICRT treatment achieved equivalent 3-year DFS and OS but low complication rate compared to CCRT treatment in early stage cervical cancer patients with intermediate-risk.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 710-710
Author(s):  
Benjamin D Fangman ◽  
Muhammad Shaalan Beg ◽  
Aravind Sanjeevaiah ◽  
Farshid Araghizadeh ◽  
Shannon Scielzo ◽  
...  

710 Background: Oncologic treatment at National Cancer Institute (NCI) designated comprehensive cancer centers improves outcomes in a variety of malignancies. Racial disparity plays an important role in cancer outcomes and prognosis. Racial outcomes were compared in early stage colorectal cancer patients that presented to a comprehensive cancer center. Methods: This is a retrospective analysis on patients diagnosed with AJCC stage II or stage III colorectal cancer and underwent surgery or adjuvant chemotherapy within the University of Texas Southwestern and Simmons Comprehensive Cancer Center. Pertinent data points were abstracted from EMR including demographic data and dates of initial diagnosis, surgery, adjuvant chemotherapy, progression, and death. Results: Between 4/2011 and 11/2015, 203 patients were identified and 167 patients had complete follow up data available. Median age of cohort was 62 (range 21-90) and most of the patients were men (52.7%). Stage II comprised 44.3% of patients while 55.7% were diagnosed at stage III. One hundred and twenty patients (71.9%) were white, while 34 patients (20.4%) identified as black and the rest belonged to other races. Hispanic ethnicity was identified in 10.4% of patients. There was no significant difference between white and black cohorts between variables age (median 62 vs. 64.5 years; p = 0.44), gender (p = 0.43), and stage (p = 0.99) of colorectal cancer. Similarly there was no significant difference between white and black race in regards to days to surgery (median 17 vs 32 days; p = 0.53), first medical oncology appointment (30 vs. 34 days; p = 0.23) and days to adjuvant chemotherapy (42 vs 52 days; p = 0.24). The rate of recurrence (10.9% vs. 26%; p = 0.09), rate of death (14.1% vs 14.7%; p = 1.0), median relapse free survival (41.7 vs. 36.2 months; p = 0.173) and median overall survival (42 vs. 38.5 months; p = 0.491) from colorectal cancer were also not significantly different between white and black races. Conclusions: Oncologic treatment at NCI designated comprehensive cancer centers may lead to racial parity in colorectal cancer outcomes. Further research should be completed to compare these results to those seen at safety net hospitals.


Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2869
Author(s):  
Laura Masfarré ◽  
Joana Vidal ◽  
Concepción Fernández-Rodríguez ◽  
Clara Montagut

Currently, the standard treatment for patients with localized colorectal cancer (CRC) includes surgical resection followed by adjuvant chemotherapy based on clinicopathological features. Recurrence risk stratification in those patients is of utmost importance to guide clinicians to avoid both under- and overtreatment. Recently, the concept of minimal residual disease (MRD) has emerged as the detection of circulating tumor DNA (ctDNA) carrying tumor-specific genomic or epigenomic alterations in the bloodstream of patients after surgery. Emerging studies described how the detection of MRD is a powerful prognostic biomarker to identify patients at higher risk of recurrence and who will potentially benefit the most from a systemic adjuvant treatment. Based on that unprecedented finding, several clinical trials involving stage II and III CRC patients are ongoing evaluating the impact of ctDNA guided treatment by escalating or deescalating adjuvant chemotherapy based on ctDNA MRD detection. This review provides a critical overview of current perspectives of liquid biopsy in early-stage CRC including technical, biological, and clinical key points, as well as ongoing ctDNA-based clinical trials that ultimately aim to improve clinical outcomes of patients with CRC.


2000 ◽  
Vol 15 (1) ◽  
pp. 51-55 ◽  
Author(s):  
A.I. Behbehani ◽  
H. Al-Sayer ◽  
M. Farghaly ◽  
N. Kanawati ◽  
A. Mathew ◽  
...  

Preoperative CEA and CA 19–9 levels have been used in the past as prognostic indicators in colorectal cancer, but Dukes’ stage is still considered to be the most important prognostic factor. Recent survival estimates may have been influenced by the fact that in the last decade adjuvant chemotherapy and postoperative irradiation have been included in the routine management of advanced-stage disease. In a heterogeneous Kuwaiti population higher reference levels (95th percentile) of CEA and CA 19–9 have been found than those usually employed. In the present study 62 patients with Dukes’ stage B + C could be analyzed for two-year disease-free survival (DFS). Relapse was observed in 19 patients, 28 patients were disease free and 15 patients with censored observations were included. No significant difference in DFS was observed in Dukes’ B (69%) versus Dukes’ C (48%) patients (p=0.09). On the other hand, Dukes’ stage B+C patients with elevated preoperative levels of CEA or CA 19–9 had a significantly poorer DFS than patients with normal levels. For CEA levels below or above the cutoff the DFS was 74% versus 23% (p=0.003); for CA 19–9 levels below or above the cutoff the DFS was 71% versus 33% (p=0.004). In 54 patients with Dukes’ stage B+C for whom preoperative levels of both CEA and CA 19–9 were available multivariate analysis revealed a decreasing risk of relapse in the following order: CEA and/or CA 19–9 elevated (chi-square 7.09; p=0.008), CA 19–9 elevated (chi-square 6.27; p=0.01), CEA elevated (chi-square 5.47; p=0.02), and Dukes’ C (chi-square 2.08; p=0.15 n.s.). Hence, novel treatment protocols may have improved the disease-free survival, but the use of adjuvant chemotherapy and/or radiotherapy is of questionable benefit in patients who have elevated levels of CEA and/or CA 19–9 prior to treatment.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16099-e16099
Author(s):  
Samvel Bardakhchyan ◽  
Sergo Mkhitaryan ◽  
Davit Zohrabyan ◽  
Liana Safaryan ◽  
Armen Avagyan ◽  
...  

e16099 Background: In Armenia colorectal cancer (CRC) is on the third place by incidence. Every year around 700 new cases are diagnosed with 60% diagnosed in 3rd and 4th stages. Methods: For this retrospective hospital-based study we have collected data from two main oncology centers in Armenia: National Oncology Center and Muratsan Hospital Complex of Yerevan state medical university. The information about patients with CRC who were treated at these two centers during 01/01/2010 - 07/01/2018 period was collected from the medical records. Results: 602 patients with CRC treated during mentioned period in these two hospitals were involved in final analysis. From them 51.8% were female. Median age at diagnosis was 58. Median follow up time was 37 months (range 3-207). 26.1% had right sided, 30.9% left sided and 43.0% rectum cancer. 8.6% of patients had stage 1, 32.9% stage 2, 38.0% stage 3, 17.6% stage 4 CRC and for 2.7% patients stage was unknown. The median survival was not reached for the entire cohort ( > 37 months). Median survival was > 66.5 months for 1st, > 48.5 months for 2nd, > 35 months for 3rd and 19 months for 4th stages. Tumor stage, grade and histology were the main independent prognostic factors by univariate and multivariate Cox regression analysis. For stage 2 CRC patients (198) we found significant difference regarding overall survival (OS) (p = 0.024) and disease free survival (DFS) (p = 0.006) for those who received adjuvant chemotherapy after surgery compared to those who didn’t receive adjuvant chemotherapy. For stage 2 and 3 rectum cancer patients, our study failed to show OS (2nd stage: p = 0.961; 3rd stage: p = 0.348) or DFS (2nd stage: p = 0.719; 3rd stage: p = 0.983) advantage for those who received radiotherapy (RT) compared with those who didn’t receive RT. In our study population 28.3% of stage 4 patients received chemotherapy combined with Bevacizumab while 70% were treated with chemotherapy only. Median OS between these two groups wasn’t significantly different (21 months in Chemo+Bevacizumab group and 18.5 months in chemo only group (p = 0.382)). 3 and 5-year survival rates were 62.9% and 51.8% for all stages combined and 79.7% and 68.5% for stages 1-2, 62.5% and 48.4% for stage 3, 24.4% and 17% for stage 4 respectively. Conclusions: As seen from our results our survival rates are inferior compared to that of developed world. The reasons for that could be compromise in surgery and RT, poor pathological assessment, unavailability of some molecular markers, poor availability of new targeted drugs and absence of national treatment guidelines.


Open Medicine ◽  
2009 ◽  
Vol 4 (4) ◽  
pp. 454-458
Author(s):  
Ahmet Alacacioglu ◽  
Baha Zengel ◽  
Ali Denecli

AbstractAdjuvant chemotherapy decreases the risk of breast cancer recurrence in patients with breast cancer. In addition, it increases the rate of survival. Therefore, various chemotherapy regimens are administered in the treatment of breast cancer. The efficacy of taxane-based adjuvant chemotherapies has been demonstrated in various trials. This trial was designed to retrospectively evaluate the efficacy of taxane-based chemotherapies in lymph node-positive, early-stage Turkish breast cancer patients. 29 patients receiving TAC regimen and 29 patients receiving AC+P regimen were evaluated. 6 courses of TAC regimen were administered every 3 weeks (docetaxel 75 mg/m2, doxorubicine 50 mg/m2, cyclophosphamide 500 mg/m2). The other patient group was administered AC+P regimen (4 courses of doxorubicin 60mg/m2, cyclophosphamide 600 mg/m2 combination every 2 weeks, followed by paclitaxel 175 mg/m2 for 4 courses every 2 weeks). The 1-year, 2-year and 3-year disease-free survival (DFS) rates were 96.3%, 81.1% and 72.8% respectively. No significant difference was detected in DFS between premenopausal and postmenopausal patients on the taxane regimen (p=0.82). There was no significant difference in DFS between estrogen or progesterone receptor positive and negative patients (p=0.46). Disease-free survival of patients receiving TAC and AC+P adjuvant chemotherapy regimen was compared. The follow-up period of patients on AC+P chemotherapy was longer than those receiving TAC (AC+P mean 38.6±12.8 months, TAC mean 17.1±5.4 months). No significant difference was observed upon evaluation of both treatment arms with respect to DFS (p=0.92). In conclusion, this trial once more demonstrated that taxane-based adjuvant chemotherapy was effective and safe in lymph node-positive, early-stage Turkish breast cancer patients.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 548-548
Author(s):  
Roberto Antonio Leon-Ferre ◽  
Jodi M Carter ◽  
David W. Hillman ◽  
Kathleen S. Tenner ◽  
David Zahrieh ◽  
...  

548 Background: sTILs are a well-established prognostic and predictive biomarker in patients with operable TNBC receiving pre or postoperative systemic therapy. We1 and others2,3 have also shown that sTILs are prognostic in patients who did not receive adjuvant chemotherapy. Here, we detail the outcomes of systemically untreated patients with N0 TNBC according to sTIL score. We focused on the N0 subset as a group of patients who may be candidates for future prospective therapy de-escalation trials. Methods: From a clinically annotated cohort of 605 patients with centrally confirmed TNBC (ER/PR < 1% and HER2 negative) with long-term outcomes data, we identified 182 patients treated with locoregional therapy only (breast surgery +/- radiation therapy and no chemotherapy). The clinicopathological characteristics of this cohort have previously been published1. In this analysis, we report the 5- and 10-year invasive disease-free survival (iDFS) and overall survival (OS) rates of patients with N0 TNBC according to sTIL levels. IDFS and OS were defined as per the STEEP classification and estimated using the Kaplan–Meier method. Comparisons of the survival distributions between groups were assessed by the log-rank test. sTILs were assessed as a continuous parameter according to the International TIL Working Group guidelines. For comparisons of outcomes between groups, tumors were classified as lymphocyte-predominant TNBC (defined as containing ≥50% sTILs) vs non-lymphocyte-predominant ( < 50% sTILs). Results: Of 182 systemically untreated patients, 149 (82%) were N0 and most (78%) were post-menopausal. T stage distribution was T1: 68%, T2: 28%, T3/4: 4%. Among N0 patients, 31 (21%) had lymphocyte-predominant TNBC, and in this group the 5-year iDFS and OS were 89% (95% CI 76-100) and 96% (95% CI 89-100), while the 10-year iDFS and OS were 89% (95% CI 76-100) and 87% (95% CI 73-100), respectively. In contrast, outcomes for patients with non-lymphocyte predominant TNBC were significantly worse. For this group, 5-year iDFS and OS were 62% (95% CI 53-73) and 78% (95% CI 71-86) while the 10-year iDFS and OS were 45% (95% CI 36-58) and 66% (95% CI 68-76), respectively ( log-rank p = 0.02 for iDFS and log-rank p = 0.03 for OS). Conclusions: sTIL quantification identifies a subset of patients with early-stage N0 TNBC with an exceedingly good prognosis, even in the absence of adjuvant chemotherapy. These data provide support for the evaluation of sTILs as part of prospective investigation of systemic therapy de-escalation strategies in N0 TNBC. References:1Leon-Ferre et al, Breast Cancer Res Treat (2018) 167:89-99 2Park et al, Ann Oncol (2019) 12:1941-1949 3De Jong et al, ESMO 2020


QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Tarek Hussein Kamel ◽  
Amr Lotfy Farag ◽  
Dr/Sherif Hassanin Ahmed ◽  
Chresteen Talaat Samy Hanna

Abstract Background Colorectal cancer (CRC) is one of the leading causes of mortality and morbidity in the world. It is the third most common malignancy after lung & breast and the fourth leading cause of cancer-related deaths worldwide, accounting for approximately 1,400,000 new cases and about 700,000 deaths worldwide. Objectives The aim of this retrospective study is to compare the epidemiology, clinicopathologic features, different treatment modalities and outcomes regarding disease free survival (DFS), progression free survival (PFS) & overall survival (OS) of colorectal cancer disease between cases presented to Ain shams university hospital & to Luxor international hospital in 3 consecutive years. Patients and Methods The study is retrospective comparative study. Clinical oncology department in Ain Shams University Hospital and Luxor International Hospital. The data Collected from January 2013 to December 2015. This study analyzed hospital records of patients who diagnosed with colorectal cancer (CRC) and allocated into two groups: Group A: CRC patients presented to Ain-Shams University Hospital from January 2013 to December 2015, group B: CRC patients presented to Luxor International Hospital from January 2013 to December 2015. Results There was no statistically significant difference regarding age parameter in LIH when compared to ASU, but the study was consistent with higher incidence in patients who were aged more than forty- accounted about 70.5% in all CRC cases. Cases less than 40 years old, in group A were 35.2%, while in Group B were 23.5%. Even there was no statistically significant difference but it may be attributable to more westernization in Lower Egypt. Other explanation may be due to decreased low socioeconomic status and different lifestyle factors in more developing region what increase risk of colorectal cancer. Among our cases, there is no statistically significant difference regarding gender between the two hospitals. Both sexes almost were affected equally, females appeared to be at a slightly higher risk of developing CRC cancer with current prevalence 1.3:1 in ASU group, and 1.1:1 in LIH group. Conclusion The need to increase awareness about CRC in Egypt especially upper Egypt, is recommended. An awareness campaign should be performed to promote detection of CRC at its earliest and most curable stage by recognizing early symptoms and enabling early referrals for colonoscopy. Those at higher risk should be offered more intensive surveillance. Similarity of the data from different centers suggests that this is the picture of colorectal cancer typical of Egypt.


BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e021341
Author(s):  
Cheng-I Hsieh ◽  
Raymond Nien-Chen Kuo ◽  
Chun-Chieh Liang ◽  
Hsin-Yun Tsai ◽  
Kuo-Piao Chung

ObjectivesOne feature unique to the Taiwanese healthcare system is the ability of physicians other than oncologists to prescribe systemic chemotherapy. This study investigated whether the care paths implemented by oncologists and non-oncologists differ with regard to patient outcomes.SettingData from the Taiwan Cancer Registry and National Health Insurance Database were linked to identify patients with colon cancer who underwent colectomy as first treatment within 3 months of diagnosis and adjuvant chemotherapy between 2005 and 2009.Participants and methodsPostoperative patients who underwent adjuvant chemotherapy were included in this study. The exclusion criteria included patients with stage IV disease, a positive surgical margin and early disease recurrence. Among the patients presenting with multiple primary cancers, we also excluded patients who were diagnosed with colon cancer but for whom this was not the first primary cancer. The variables included sex, age, comorbidities, disease stage, chemotherapy cycle and changes in treatment regimen as well as the specialty of treatment providers and their case volume. Cox regression models and Kaplan-Meier analysis were used to examine differences in outcomes in the matched cohorts.ResultsWe examined 3534 patients who were prescribed adjuvant chemotherapy by physicians from different disciplines. In terms of 5-year disease-free survival, no significant difference was observed between the groups of oncologists or surgeons among patients with stage II (90.02%vs88.99%) or stage III (77.64%vs79.99%) diseases. Patients who were subjected to changes in their chemotherapy regimens presented recurrence rates higher than those who were not.ConclusionsThe discipline of practitioners is seldom taken into account in most series. This is the first study to provide empirical evidence demonstrating that the outcomes of patients with colon cancer do not depend on the treatment path, as long as the selection criteria for adjuvant chemotherapy is appropriate. Further study will be required before making any further conclusions.


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