Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm

Ryan, Éanna J; Creavin, Ben; Sheahan, Kieran

doi:10.3389/fonc.2020.01369

Cited by 16 publications

(15 citation statements)

References 149 publications

(196 reference statements)

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“…Next, the correlation between the degree of histologic response to nCRT and IS B was evaluated. Several classification can assess the degree of histologic response: i/the NAR score [108]: calculated using the equation [5pN-3(cT-pT) + 12] 2 /9.61, and classified as low (<8), intermediate (8)(9)(10)(11)(12)(13)(14)(15)(16), and high (>16), ii/ the Dworak classification [109] defined as complete (Dworak 4), near complete (Dworak 3), moderate (Dworak 2), minimal (Dworak 1), and no regression (Dworak 0) (Figure 1B), and iii/ypTNM staging i.e., the postsurgical pathologic T and N evaluation. IS B was correlated to nCRT response assessed by these three classifications (P < 0.001).…”

Section: Immunoscore Biopsy (Is B ): a Derived Immunoscorementioning

confidence: 99%

The “Immunoscore” in rectal cancer: could we search quality beyond quantity of life?

et al. 2022

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Because of the function and anatomical environment of the rectum, therapeutic strategies for local advanced rectal cancer (LARC) must deal with two challenging stressors that are a high-risk of local and distal recurrences and a high-risk of poor quality of life (QoL). Over the last three decades, advances in screening tests, therapies, and combined-modality treatment options and strategies have improved the prognosis of patients with LARC. However, owing to the heterogeneous nature of LARC and genetic status, the patient may not respond to a specific therapy and may be at increased risk of side-effects without the life-prolonging benefit. Indeed, each therapy can cause its own side-effects, which may worsen by a combination of treatments resulting in long-term poor QoL. In LARC, QoL has become even more essential with the increasing www.oncotarget.com incidence of rectal cancer in young individuals. Herein, we analyzed the value of the Immunoscore-Biopsy (performed on tumor biopsy at diagnosis) in predicting outcomes, alone or in association with clinical and imaging data, for each therapy used in LARC.

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Section: Immunoscore Biopsy (Is B ): a Derived Immunoscorementioning

confidence: 99%

The “Immunoscore” in rectal cancer: could we search quality beyond quantity of life?

et al. 2022

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“…In Spain, the total number of new cases is estimated to be more than 44,000 each year, and reaches around 14.6% of total deaths from cancer annually [ 1 , 2 ]. Approximately, almost one-third of all newly diagnosed CRCpatients have rectal tumors [ 3 ]. Of note, locally advanced rectal cancer (LARC) has been progressively considered and treated as an independent disease due to several factors such as its primarily extra peritoneal location, high local recurrence risk and differences in metastatic behavior [ 3 , 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

“…Approximately, almost one-third of all newly diagnosed CRCpatients have rectal tumors [ 3 ]. Of note, locally advanced rectal cancer (LARC) has been progressively considered and treated as an independent disease due to several factors such as its primarily extra peritoneal location, high local recurrence risk and differences in metastatic behavior [ 3 , 4 , 5 ]. Over the last few decades, several studies have explored different treatment strategies to improve the outcome of LARC patients, leading to significant changes in the clinical management of this disease [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Validation of microRNA-199b as A Promising Predictor of Outcome and Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer Patients

Cristóbal

Santos

Rubio

et al. 2021

Cancers

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The absence of established predictive markers with value to anticipate response to neoadjuvant 5-fluorouracil (5-FU)-based chemoradiotherapy (CRT) represents a current major challenge in locally advanced rectal cancer (LARC). The tumor suppressor microRNA (miR)-199b has been reported to play a key role determining 5-FU sensitivity of colorectal cancer cells through the regulation of several signaling pathways, and has emerged as a novel molecular target to overcome the 5-FU resistant phenotype. Moreover, miR-199b downregulation was described as a common alteration that predicts lack of response to preoperative CRT in LARC but this issue needs to be confirmed in independent larger cohorts. Here, we evaluate the clinical impact of miR-199b in LARC and perform additional analyses to further clarify its potential relevance as novel marker in this disease. Thus, miR-199b expression was quantified by real-time-PCR in a cohort of 185 LARC patients, observing this miR downregulated in 22.2% of cases and significantly associated with higher tumor size (p= 0.026) and positive lymph node after CRT (p= 0.005), and higher pathological stage (p= 0.004). Notably, this alteration showed a strong independent predictive value of poor pathological response to neoadjuvant CRT (p= 0.004). Moreover, the subgroup of cases with low miR-199b levels had a markedly shorter overall (p< 001) and event-free survival (p< 0.001), and multivariate analyses showed that miR-199b deregulation represents an independent prognosticator for patient outcome in LARC. Interestingly, the prognostic impact of this miR was strongly significant in both younger and elderly patients, and was very effective determining patient recurrence (p= 0.004). Finally, we compared miR-199b expression profiles in a set of cases with pre and post-treatment samples available, observing that only a minimal response leads to miR-199b increase levels, further suggesting its potential clinical and therapeutic relevance as a promising marker and novel molecular target for the management of LARC.

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“…The development of accurate tools to better select patients to more aggressive therapy is paramount in rectal carcinoma. Given the need to stratify patients into responders and non-responders to NCRT prior to its onset, improving the selection of those most likely to obtain a pathological complete response (pCR), several studies have evaluated possible biomarkers, which allow the dynamic monitoring of the disease [ 12 , 13 ]. However, the results are still controversial with limitations for use in clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Silva

Abdallah

Flores

et al. 2021

Cells

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The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

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Delivery of Personalized Care for Locally Advanced Rectal Cancer: Incorporating Pathological, Molecular Genetic, and Immunological Biomarkers Into the Multimodal Paradigm

Cited by 16 publications

References 149 publications

The “Immunoscore” in rectal cancer: could we search quality beyond quantity of life?

The “Immunoscore” in rectal cancer: could we search quality beyond quantity of life?

Validation of microRNA-199b as A Promising Predictor of Outcome and Response to Neoadjuvant Treatment in Locally Advanced Rectal Cancer Patients

Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

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