Dataset Information

Radiosensitivity of Cancer Stem Cells Has Potential Predictive Value for Individual Responses to Radiotherapy in Locally Advanced Rectal Cancer.

ABSTRACT: Neo-adjuvant radiotherapy is frequently employed in the therapeutic management of locally advanced rectal cancer (LARC). Radiotherapy can both reduce local recurrence and improve the success of surgical procedures by reducing tumor mass size. However, some patients show a poor response to treatment, which results in primary resistance or relapse after apparent curative surgery. In this work, we report in vitro and in vivo models based on patient-derived cancer stem cells (CSCs); these models are able to predict individual responses to radiotherapy in LARC. CSCs isolated from colorectal cancer biopsies were subjected to in vitro irradiation with the same clinical protocol used for LARC patients. Animal models, generated by CSC xenotransplantation, were also obtained and treated with the same radiotherapy protocol. The results indicate that CSCs isolated from rectal cancer needle biopsies possess an intrinsic grade of sensitivity to treatment, which is also maintained in the animal model. Notably, the specific CSCs' in vitro and in vivo sensitivity values correspond to patients' responses to radiotherapy. This evidence suggests that an in vitro radiotherapy response predictivity assay could support clinical decisions for the management of LARC patients, thus avoiding radiation toxicity to resistant patients and reducing the treatment costs.

SUBMITTER: Puglisi C

PROVIDER: S-EPMC7762426 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Radiosensitivity of Cancer Stem Cells Has Potential Predictive Value for Individual Responses to Radiotherapy in Locally Advanced Rectal Cancer.

Puglisi Caterina C Giuffrida Raffaella R Borzì Giuseppina G Di Mattia Paolo P Costa Anna A Colarossi Cristina C Deiana Enrica E Picardo Maria Carolina MC Colarossi Lorenzo L Mare Marzia M Marino Lorenza L Di Grazia Alfio A Forte Stefano S

Cancers 20201207 12

Neo-adjuvant radiotherapy is frequently employed in the therapeutic management of locally advanced rectal cancer (LARC). Radiotherapy can both reduce local recurrence and improve the success of surgical procedures by reducing tumor mass size. However, some patients show a poor response to treatment, which results in primary resistance or relapse after apparent curative surgery. In this work, we report in vitro and in vivo models based on patient-derived cancer stem cells (CSCs); these models are ...[more]

PMID: 33297488

Similar Datasets

Project description:BackgroundWe examined the predictive value of mismatch repair (MMR) status in relation to responses to neoadjuvant therapy and the prognosis of locally advanced rectal cancer patients.MethodsA total of 854 consecutive patients with locally advanced rectal cancer with MMR status who underwent neoadjuvant therapy followed by curative surgery between January 2013 and December 2018 were included this retrospective study. MMR status was determined by an analysis of MMR protein expression by immunohistochemistry (IHC). Propensity score matching was performed to reduce imbalances in baseline characteristics. The categorical variables were compared using the Chi-square test or Fisher's exact test. Local recurrence-free survival (LRFS) and disease-free survival (DFS) curves were estimated using the Kaplan-Meier method.ResultsDeficient MMR (dMMR) was detected in 63 of the 854 (7.4%) patients. Patients with dMMR had a lower proportion of tumor regression grade (TRG) of 0-1 compared with proficient MMR (pMMR) (28.6% vs. 43.7%; P=0.027). After propensity score matching at 1:4 for patients who received chemotherapy alone, proportion of TRG of 0-1 was observed to be significantly lower in dMMR than pMMR patients (9.1 vs. 30.3%%; P=0.013). For patients who received chemoradiation, after matching, no significant difference in the proportion of TRG 0-1 and the pathological complete response (pCR) rate was observed. The multivariable analysis revealed that patients whose tumors had dMMR had significantly longer DFS than those whose tumors had pMMR [hazards ratio (HR) =0.38, 95% confidence interval (CI): 0.18-0.81, P=0.013]. In the subgroup analysis, dMMR was only a statistically significant prognostic factor for DFS in patients with ypStage II/III (HR =0.38, 95% CI: 0.17-0.86; P=0.020).ConclusionsWe found that patients with dMMR responded worse to chemotherapy alone than patients with pMMR, in terms of TRG. Also, dMMR is a good prognostic marker for DFS in patients with ypStage II/III after neoadjuvant therapy.

Project description:BackgroundPatients (pts) affected with locally advanced rectal cancer (LARC) may respond differently to neoadjuvant chemoradiotherapy (nCRT). The identification of reliable biomarkers able to predict oncological outcomes could help in the development of risk-adapted treatment strategies. It has been suggested that inflammation parameters may have a role in predicting tumor response to nCRT and survival outcomes and in rectal cancer, but no definitive conclusion can be drawn at present. The aim of the current study is to evaluate the role of baseline inflammatory markers as prognostic and predictive factors in a large multicentric Italian cohort of LARC pts.MethodsPatients diagnosed with LARC from January 2002 to December 2019 in 9 Italian centers were retrospectively collected. Patients underwent long-course RT with chemotherapy based on fluoropyrimidine ± oxaliplatin followed by surgery. Inflammatory markers were retrieved based on a pre-treatment blood sample including HEI (hemo-eosinophils inflammation index), SII (systemic index of inflammation), NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio) and MLR (monocyte-to-lymphocyte ratio). Outcomes of interest were pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS).Results808 pts were analyzed. pCR rate was 22 %, 5yOS and 5yDFS were 84.0% and 63.1% respectively. Multivariate analysis identified that a NLR cut-off value >1.2 and SII cut-off value >500 could predict pCR (p = 0.05 and 0.009 respectively). In addition to age, extramesorectal nodes and RT dose, MLR >0.18 (p = 0.03) and HEI = 3 (p = 0.05) were independent prognostic factors for DFS. Finally, age, RT dose, MLR with a cut-off >0.35 (p = 0.028) and HEI = 3 (p = 0.045) were independent predictors of OS.ConclusionsHigher values of baseline composite inflammatory markers can serve as predictors of lower pCR rates and worse survival outcomes in LARC patients undergoing nCRT. More reliable data from prospective studies could lead to the integration of these inexpensive and easy-to-derive tools into clinical practice.

Dataset Information

Radiosensitivity of Cancer Stem Cells Has Potential Predictive Value for Individual Responses to Radiotherapy in Locally Advanced Rectal Cancer.

Publications

Radiosensitivity of Cancer Stem Cells Has Potential Predictive Value for Individual Responses to Radiotherapy in Locally Advanced Rectal Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets