The potential of circulating tumor DNA (ctDNA) to guide adjuvant chemotherapy decision making in locally advanced rectal cancer (LARC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3521-3521 ◽  
Author(s):  
Jeanne Tie ◽  
Joshua Cohen ◽  
Yuxuan Wang ◽  
Lu Li ◽  
Isaac Kinde ◽  
...  
Keyword(s):  
Decision Making ◽  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Clinical Decision Making ◽  
Locally Advanced ◽  
Recurrence Risk ◽  
Routine Practice ◽  
Plasma Samples ◽  
Multi Centre Study ◽  
Ctdna Analysis

3521 Background: The optimal approach to adjuvant chemotherapy for rectal cancer is keenly debated. Routine practice and clinical guidelines vary widely. After pre-operative chemoradiation (CRT), a pathologic complete response (pCR) or nodal involvement (pN+) are prognostic markers that can guide clinical decision-making, but markers that better define the patients (pts) that are likely or unlikely to benefit from chemotherapy are urgently needed. We investigated the potential role of ctDNA as a biomarker to guide therapy. Methods: We conducted a prospective, multi-centre study in pts with LARC (T3/T4 and/or N+) planned for CRT and curative resection. Serial plasma samples were collected pre-CRT, post-CRT, and 4-10 weeks after surgery. Somatic mutations in individual pts’ tumor were identified via sequencing of 15 genes commonly mutated in colorectal cancers. We then designed personalized assays to quantify ctDNA in plasma samples. Pts received adjuvant therapy at clinician discretion. Results: 200 pts were enrolled between Apr-2012 and Dec-2015. Median age was 62 years (range 28-86), 67% were male and 159 pts had pre-CRT and post-op ctDNA samples available for analysis. Of these, 122 (77%) pts had detectable ctDNA prior to therapy. After surgery, 19 pts had detectable ctDNA and 11 of these 19 (58%) have recurred during a median follow up of 22 months. Recurrence occurred in only 12 of 140 (8.6%) with negative ctDNA (HR 12, p < 0.001). One hundred and two (64%) pts received adjuvant chemotherapy. Post-op ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy (chemo: HR 10, p < 0.001; no chemo: HR 16, p < 0.001). Thirty-four pts (21%) achieved a pCR, 43 (27%) had pN+ disease. pCR (vs non-pCR) was associated with a trend for lower recurrence risk (HR 0.31, p = 0.089) and pN+ (vs pN0) with a higher recurrence risk (HR 4.2, p < 0.001). ctDNA detection remained predictive of recurrence among pts with a pCR (HR 14, p = 0.014) or with pN+ disease (HR 11, p < 0.001). Conclusions: Post-op ctDNA analysis stratifies pts with LARC into very high and low risk groups. ctDNA analysis remains strongly predictive of recurrence among pts with both lower risk (pCR) and higher risk (pN+) disease.

scholarly journals Serial circulating tumour DNA analysis during multimodality treatment of locally advanced rectal cancer: a prospective biomarker study

Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 663-671 ◽  
Author(s):  
Jeanne Tie ◽  
Joshua D Cohen ◽  
Yuxuan Wang ◽  
Lu Li ◽  
Michael Christie ◽  
...  
Keyword(s):  
Risk Factors ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Recurrence Free Survival ◽  
Plasma Samples ◽  
Free Survival ◽  
Ctdna Analysis ◽  
Circulating Tumour Dna

ObjectiveFor patients with locally advanced rectal cancer (LARC), adjuvant chemotherapy selection following surgery remains a major clinical dilemma. Here, we investigated the ability of circulating tumour DNA (ctDNA) to improve risk stratification in patients with LARC.DesignWe enrolled patients with LARC (T3/T4 and/or N+) planned for neoadjuvant chemoradiotherapy. Plasma samples were collected pretreatment, postchemoradiotherapy and 4–10 weeks after surgery. Somatic mutations in individual patient’s tumour were identified via massively parallel sequencing of 15 genes commonly mutated in colorectal cancer. We then designed personalised assays to quantify ctDNA in plasma samples. Patients received adjuvant therapy at clinician discretion, blinded to the ctDNA results.ResultsWe analysed 462 serial plasma samples from 159 patients. ctDNA was detectable in 77%, 8.3% and 12% of pretreatment, postchemoradiotherapy and postsurgery plasma samples. Significantly worse recurrence-free survival was seen if ctDNA was detectable after chemoradiotherapy (HR 6.6; P<0.001) or after surgery (HR 13.0; P<0.001). The estimated 3-year recurrence-free survival was 33% for the postoperative ctDNA-positive patients and 87% for the postoperative ctDNA-negative patients. Postoperative ctDNA detection was predictive of recurrence irrespective of adjuvant chemotherapy use (chemotherapy: HR 10.0; P<0.001; without chemotherapy: HR 22.0; P<0.001). Postoperative ctDNA status remained an independent predictor of recurrence-free survival after adjusting for known clinicopathological risk factors (HR 6.0; P<0.001).ConclusionPostoperative ctDNA analysis stratifies patients with LARC into subsets that are either at very high or at low risk of recurrence, independent of conventional clinicopathological risk factors. ctDNA analysis could potentially be used to guide patient selection for adjuvant chemotherapy.

Adjuvant chemotherapy following neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 626-626
Author(s):  
Kirsten Elizabeth Jean Laws ◽  
Christina Wilson ◽  
David McIntosh ◽  
Stephen Harrow
Keyword(s):  
Decision Making ◽  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Treatment ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Number Of Patients ◽  
Pre Treatment

626 Background: Established guidelines exist for indications of adjuvant chemotherapy in colon cancer. However, in patients receiving neoadjuvant chemoradiotherapy for locally advanced rectal cancer, the benefit of adjuvant chemotherapy remains unproven. We evaluated clinical decision making behind adjuvant chemotherapy for locally advanced rectal cancer patients in our institute. Methods: Patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified. Exclusion criteria were inoperable disease, postoperative, recurrence, or palliative intent. 231 cases were examined retrospectively for the decisions behind giving or withholding adjuvant chemotherapy. Results: 35 (15%) were ineligible for consideration of adjuvant chemotherapy due to disease progression. 38 patients (16.4%) received chemotherapy in the adjuvant setting and 158 patients (68.4%) were potentially eligible for adjuvant chemotherapy, but did not receive it. The majority of clinicians based their decisions on post operative pathology results, and the key factor in decision making was final pathological stage in 65%. Clinicians considered pre-treatment imaging a key factor in only 14% of cases, despite a considerable number of patients being downstaged from a potentially higher initial pre-treatment stage that could have warranted adjuvant treatment. A considerable number of patients (25%) were deemed unfit for adjuvant treatment following neoadjuvant chemoradiotherapy and surgery due to toxicity of combined treatment. Conclusions: This analysis highlights the difficulty in clinical decision making for adjuvant chemotherapy in rectal cancer. The accuracy of pre-treatment staging is difficult to ascertain and its use to justify post operative treatment uncertain. It appears the majority of clinicians in our institute base their decision on post operative pathology. A considerable number of patients were not fit for consideration of adjuvant treatment due to toxicity of previous treatment. Further research is warranted as to the benefits of adjuvant chemotherapy, particularly in a setting where prior treatment already causes significant toxicity.

scholarly journals Prognostic Genomic Tissue-Based Biomarkers in the Treatment of Localized Prostate Cancer

2022 ◽  
Vol 12 (1) ◽  
pp. 65
Author(s):  
Gianluca Ingrosso ◽  
Emanuele Alì ◽  
Simona Marani ◽  
Simonetta Saldi ◽  
Rita Bellavita ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Decision Making ◽  
Clinical Decision Making ◽  
Positive Impact ◽  
Wide Spectrum ◽  
Locally Advanced ◽  
Treatment Strategies ◽  
Quality Criteria ◽  
Localized Prostate Cancer ◽  
Decision Making Process

In localized prostate cancer clinicopathologic variables have been used to develop prognostic nomograms quantifying the probability of locally advanced disease, of pelvic lymph node and distant metastasis at diagnosis or the probability of recurrence after radical treatment of the primary tumor. These tools although essential in daily clinical practice for the management of such a heterogeneous disease, which can be cured with a wide spectrum of treatment strategies (i.e., active surveillance, RP and radiation therapy), do not allow the precise distinction of an indolent instead of an aggressive disease. In recent years, several prognostic biomarkers have been tested, combined with the currently available clinicopathologic prognostic tools, in order to improve the decision-making process. In the following article, we reviewed the literature of the last 10 years and gave an overview report on commercially available tissue-based biomarkers and more specifically on mRNA-based gene expression classifiers. To date, these genomic tests have been widely investigated, demonstrating rigorous quality criteria including reproducibility, linearity, analytical accuracy, precision, and a positive impact in the clinical decision-making process. Albeit data published in literature, the systematic use of these tests in prostate cancer is currently not recommended due to insufficient evidence.

scholarly journals The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7040 ◽  
Author(s):  
Fatima Domenica Elisa De Palma ◽  
Gaetano Luglio ◽  
Francesca Paola Tropeano ◽  
Gianluca Pagano ◽  
Maria D’Armiento ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Decision Making ◽  
Locally Advanced ◽  
Therapy Response ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Clinical Decision ◽  
Locally Advanced Rectal Cancer ◽  
Specific Expression ◽  
Micro Rnas

The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, microRNAs (miRNAs) seem to be promising candidates for predicting LARC prognosis and/or therapy response, particularly due to their stability, facile detection, and disease-specific expression in human tissues, blood, serum, or urine. Although a considerable number of studies involving potential miRNA predictors to nCRT have been conducted over the years, to date, the identification of the perfect miRNA signatures or single miRNA, as well as their use in the clinical practice, is still representing a challenge for the management of LARC patients. In this review, we will first introduce LARC and its difficult management. Then, we will trace the scientific history and the key obstacles for the identification of specific miRNAs that predict responsiveness to nCRT. There is a high potential to identify non-invasive biomarkers that circulate in the human bloodstream and that might indicate the LARC patients who benefit from the watch-and-wait approach. For this, we will critically evaluate recent advances dealing with cell-free nucleic acids including miRNAs and circulating tumor cells as prognostic or predictive biomarkers.

Pilot Study of Patients’ Preferences for Immediate Resection Versus a Watch and Wait Approach After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

2020 ◽  
pp. OP.20.00158
Author(s):  
Ashray Gunjur ◽  
Grace Chazan ◽  
Genni Newnham ◽  
Sue-Anne McLachlan
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Recurrence Risk ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Watch And Wait ◽  
Time Tradeoff

PURPOSE: In patients with rectal cancer who achieve a clinical complete response to neoadjuvant chemoradiation, it may be reasonable to adopt a watch-and-wait (W&W) strategy rather than proceed to immediate resection of the rectum. Patient preferences for this strategy are unknown. The primary aim of the current study was to determine the feasibility of assessing hypothetical recurrence and survival differences that relevant patients would tolerate to avoid immediate resection of the rectum. A secondary aim included estimating patients’ tolerance thresholds and the factors that might predict them. METHODS: We developed a study-specific written questionnaire based on a previously validated instrument. Hypothetical time tradeoff tasks were used to determine the recurrence rate patients would accept to adopt a W&W strategy and the survival benefit that would be needed to justify choosing immediate resection over W&W. Feasibility was measured on the basis of response rate, the stated ease of completion and the satisfaction of task, and time used. RESULTS: Twenty of 31 potentially eligible patients completed the study-specific questionnaire. The majority of respondents felt that questions were clear (70%) and not hard to understand (65%). The median acceptable recurrence risk to adopt a W&W strategy was 20% (interquartile range [IQR], 10%-35%). Patients required a median of 2.0 extra years of survival (IQR, 1.0-3.0 years) over a baseline 7.0 years, and they required a median extra 10% (IQR, 4%-19%) over baseline 70% survival rates to justify immediate resection. CONCLUSION: Measuring the preferences of patients with rectal cancer using time tradeoff methods seemed to be feasible. Larger studies are needed to confirm how acceptable a W&W strategy would be for relevant patients.

scholarly journals Is It Possible to Shorten the Duration of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

Medicine ◽  
2016 ◽  
Vol 95 (16) ◽  
pp. e3427 ◽  
Author(s):  
Kai-Yun You ◽  
Rong Huang ◽  
Xin Yu ◽  
Yi-Min Liu ◽  
Yuan-Hong Gao
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer
Sign in / Sign up

Export Citation Format

Share Document