The role of circulating tumor cells and K-ras mutations in patients with locally advanced rectal cancer: a prospective study

Bahnassy, Abeer A.; Abdelazim, Yasser; Ezzat, Somaya; Abdellateif, Mona S.; Zekri, Abdel‐Rahman N.; Mohanad, Marwa; Salama, A.E.; Khaled, Hussein

doi:10.1007/s11033-020-05973-8

Cited by 7 publications

(5 citation statements)

References 23 publications

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“…However, few studies have investigated the role of KRAS mutations in patients with LARC. Our results showed that KRAS mutations were present in 24.7% of patients, a lower frequency than reported in other publications [ 20 , 21 , 22 ]. In our study, we found that KRAS mutations were significantly associated with poorer OS and PFS in LARC patients receiving nCRT, but there was no relation between KRAS mutations and TRG.…”

Section: Discussioncontrasting

confidence: 80%

Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy

Carnicero

Ramalle-Gómara²,

Rubio-Mediavilla

et al. 2022

JCM

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Neoadjuvant chemoradiotherapy (CRT) is one of the standards of care in locally advanced rectal cancer (LARC). This retrospective study examines clinical, analytical, and pathological parameters collected from 77 patients with locally advanced (cT3-4 or cN+) rectal carcinoma diagnosed between 2007 and 2017 at our institution that were treated with preoperative CRT and surgery. In the prognosis analysis, lower hemoglobin levels (p = 0.008), lower lymphocyte/monocyte ratio (LMR) (p = 0.011), and higher platelet/lymphocyte ratio (PLR) (p = 0.029) in the second determination (Hb2, LMR2 and PLR2) were associated with the relapse group. The number of positive nodes after surgery (N+) showed a statistically significant association with relapse (p = 0.012). KRAS mutations were associated with a worse prognosis for 5 years progression-free and overall survival (p = 0.005 and 0.022; respectively). We propose a prognostic model based on four parameters (number of positive lymph nodes after surgery, hemoglobin levels, LMR, and PLR after neoadjuvant therapy) that can be a useful tool to estimate relapse risk. Moreover, bilirubin could be a useful parameter to predict the response to neoadjuvant CRT.

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Section: Discussioncontrasting

confidence: 80%

Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy

Carnicero

Ramalle-Gómara²,

Rubio-Mediavilla

et al. 2022

JCM

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“…Firstly, the patient had a K-RAS mutation. As the most common and first discovered mutation in colorectal cancer, KRAS mutations are seen in between 30% and 40% of cases and are often considered a poor prognostic indicator ( 20 , 21 ). On one hand, KRAS mutant cancers are highly invasive ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Long-term survival of a patient with advanced rectal cancer and multiple pelvic recurrences after seven surgeries

et al. 2023

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BackgroundRectal cancer has a high risk of recurrence and metastasis, with median survival ranging from 24 months to 36 months. K-RAS mutation is a predictor of poor prognosis in rectal cancer. Advanced rectal cancer can be stopped in its tracks by pelvic exenteration.Case summaryA 51-year-old woman was diagnosed with advanced rectal cancer (pT4bN2aM1b, stage IV) with the KRAS G12D mutation due to a change in bowel habits. The patient had experienced repeated recurrences of rectal cancer after initial radical resection, and the tumor had invaded the ovaries, sacrum, bladder, vagina and anus. Since the onset of the disease, the patient had undergone a total of seven surgeries and long-term FOLFIRI- or XELOX-based chemotherapy regimens, with the targeted agents bevacizumab and regorafenib. Fortunately, the patient was able to achieve intraoperative R0 resection in almost all surgical procedures and achieve tumor-free survival after pelvic exenteration. The patient has been alive for 86 months since her diagnosis.ConclusionsPatients with advanced rectal cancer can achieve long-term survival through active multidisciplinary management and R0 surgery.

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“…Both are proofed as surrogate markers in other malignancies, but their role in response assessment of rectal cancer remains still unclear. [24][25][26] Longitudinal trends could serve as surrogate for therapy response. [25] Additionally, we focus on treatment-related changes of surface proteins (e.g., programmed death ligand 1 [PD-L1]).…”

Section: The Clinical Trial Is Registered At Clinicaltrialsgov (Id: N...mentioning

confidence: 99%

Planning adaptive treatment by longitudinal response assessment implementing MR imaging, liquid biopsy and analysis of microenvironment during neoadjuvant treatment of rectal cancer (PRIMO)

et al. 2023

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Introduction: Conducting neoadjuvant chemoradiotherapy (CRT) and additional preoperative consolidating chemotherapy (CTx), that is, total neoadjuvant therapy (TNT), improves local control and complete response (CR) rates in locally advanced rectal cancer (LARC), putting the focus on organ preservation concepts. Therefore, assessing response before surgery is crucial. Some LARC patients would either not benefit from intensification by TNT or may reach CR, making resection not mandatory. Treatment of LARC should therefore be based on patient individual risk and response to avoid overtreatment.The "PRIMO" pilot study aims to determine early response assessment to form a basis for development and validation of a noninvasive response prediction model by a subsequent prospective multicenter trial, which is highly needed for individual, response-driven therapy adaptions.Methods: PRIMO is a prospective observational cohort study including adult patients with LARC receiving neoadjuvant CRT. At least 4 multiparametric magnetic resonance imaging (MRI) scans (diffusion-weighted imaging [DWI] and hypoxia-sensitive sequences) as well as repeated blood samples in order to analyze circulating tumor cells (CTC) and cell-free tumor DNA (ctDNA) are scheduled. Pelvic radiotherapy (RT, 50.4 Gy) will be performed in combination with a 5-fluorouracil/oxaliplatin regimen in all patients (planned: N = 50), succeeded by consolidation CTx (FOLFOX4) if feasible. Additional (immuno)histochemical markers, such as tumor-infiltrating lymphocytes (TIL) and programmed death ligand 1 (PD-L1) status will be analyzed before and after CRT. Routine resection is scheduled subsequently, nonoperative management is offered alternatively in case of clinical CR (cCR).The primary endpoint is pathological response; secondary endpoints comprise longitudinal changes in MRI as well as in CTCs and TIL. These are evaluated for early response prediction during neoadjuvant therapy, in order to develop a noninvasive response prediction model for subsequent analyses.Discussion: Early response assessment is the key in differentiating "good" and "bad" responders during neoadjuvant CRT, allowing adaption of subsequent therapies (additional consolidating CTx, organ preservation). This study will contribute in this regard, by advancing MR imaging and substantiating new surrogate markers. Adaptive treatment strategies might build on these results in further studies. Abbreviations: (c/p)CR = (clinical/pathological) complete response, ctDNA = cell-free tumor DNA, ARO = Arbeitsgemeinschaft Radiologische Onkologie of DKG (Radiation Oncology working group German Cancer Society), CRT = chemoradiotherapy, CTC = circulating tumor cell, CTx = chemotherapy, DWI = diffusion-weighted imaging, LARC = locally advanced rectal cancer, MRI = magnetic resonance imaging, NAR = Neoadjuvant Rectal Score, PD-L1 = programmed death ligand 1, QoL = quality of life, RT = radiotherapy, TIL = tumor-infiltrating lymphocytes, TNT = total neoadjuvant therapy, TRG = tumor regression grading.

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The role of circulating tumor cells and K-ras mutations in patients with locally advanced rectal cancer: a prospective study

Cited by 7 publications

References 23 publications

Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy

Prognostic and Predictive Biomarkers in Patients with Locally Advanced Rectal Cancer (LARC) Treated with Preoperative Chemoradiotherapy

Case Report: Long-term survival of a patient with advanced rectal cancer and multiple pelvic recurrences after seven surgeries

Planning adaptive treatment by longitudinal response assessment implementing MR imaging, liquid biopsy and analysis of microenvironment during neoadjuvant treatment of rectal cancer (PRIMO)

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