Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Damilakis, Emmanouil; Mavroudis, Dimitriοs; Sfakianaki, Maria; Souglakos, John

doi:10.3390/cancers12040889

Cited by 21 publications

(17 citation statements)

References 91 publications

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“…The analyzed MRI data included T1W [ 36 ], T2W [ 25 ] and DWI [ 24 ] images from pre-treatment to post-treatment [ 44 ]. However, few of them focused on CT-based radiomics analysis, although it has been demonstrated that multiple radiomics analysis based on CT images can facilitate the prediction of lymph node metastasis [ 37 , 49 , 50 ], distant metastasis [ 51 ], therapy response [ 52 , 53 ] and prognostic outcomes [ 28 ]. Two previous studies have performed CT-based radiomics analysis for pCR prediction but came out with controversial results [ 27 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Radiomic signature of the FOWARC trial predicts pathological response to neoadjuvant treatment in rectal cancer

Zhuang

Liu

et al. 2021

J Transl Med

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Background We aimed to develop a radiomic model based on pre-treatment computed tomography (CT) to predict the pathological complete response (pCR) in patients with rectal cancer after neoadjuvant treatment and tried to integrate our model with magnetic resonance imaging (MRI)-based radiomic signature. Methods This was a secondary analysis of the FOWARC randomized controlled trial. Radiomic features were extracted from pre-treatment portal venous-phase contrast-enhanced CT images of 177 patients with rectal cancer. Patients were randomly allocated to the primary and validation cohort. The least absolute shrinkage and selection operator regression was applied to select predictive features to build a radiomic signature for pCR prediction (rad-score). This CT-based rad-score was integrated with clinicopathological variables using gradient boosting machine (GBM) or MRI-based rad-score to construct comprehensive models for pCR prediction. The performance of CT-based model was evaluated and compared by receiver operator characteristic (ROC) curve analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare CT-based rad-score, MRI-based rad-score and the combined rad-score. Results We developed a CT-based rad-score for pCR prediction and a gradient boosting machine (GBM) model was built after clinicopathological variables were incorporated, with improved AUCs of 0.997 [95% CI 0.990–1.000] and 0.822 [95% CI 0.649–0.995] in the primary and validation cohort, respectively. Moreover, we constructed a combined model of CT- and MRI-based radiomic signatures that achieve better AIC (75.49 vs. 81.34 vs.82.39) than CT-based rad-score (P = 0.005) and MRI-based rad-score (P = 0.003) alone did. Conclusions The CT-based radiomic models we constructed may provide a useful and reliable tool to predict pCR after neoadjuvant treatment, identify patients that are appropriate for a 'watch and wait' approach, and thus avoid overtreatment. Moreover, the CT-based radiomic signature may add predictive value to the MRI-based models for clinical decision making.

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Section: Discussionmentioning

confidence: 99%

Radiomic signature of the FOWARC trial predicts pathological response to neoadjuvant treatment in rectal cancer

Zhuang

Liu

et al. 2021

J Transl Med

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“…Although recently, rapid development has been made in the field of immunotherapy ( 14 , 15 ), the first-line standard treatment for metastatic colorectal cancer (mCRC) is 5FU-based chemotherapies, with or without anti-angiogenic agents. ICI monotherapy is efficacious in the treatment of mCRC with dMMR/MSI-H.…”

Section: Discussionmentioning

confidence: 99%

Preliminary Efficacy and Safety of Camrelizumab in Combination With XELOX Plus Bevacizumab or Regorafenib in Patients With Metastatic Colorectal Cancer: A Retrospective Study

et al. 2021

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BackgroundFor a majority of patients with metastatic colorectal cancer (mCRC) with MS stable (MSS) or mismatch repair proficient (pMMR), the role of immunotherapy is undetermined. This study investigated the efficacy and safety of camrelizumab when added to XELOX chemotherapy plus bevacizumab or regorafenib as first-line therapy for mCRC.Materials and MethodsMedical records of mCRC patients who received camrelizumab and XELOX plus bevacizumab or regorafenib at the First Hospital of Quanzhou Affiliated to Fujian Medical University between June 1, 2019, and April 30, 2021, were retrospectively collected. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and side effects of the drug were recorded and reviewed.ResultsTwenty-five eligible patients received combination therapy, including bevacizumab in 19 patients and regorafenib in 6. Twenty-one patients had pMMR/MSS and one MSI-H. Of the 25 patients who could be evaluated for efficacy, 18 (72%) achieved PR, 6 (24%) achieved SD, and 1 (4%) achieved PD. The ORR and DCR were 72% (18/25) and 96% (24/25), respectively. The median progression-free survival (PFS) was 11.2 months (95% CI 8.9–13.9), and OS had not yet been reached. The combination regimen of regorafenib in six (24%) patients was unassociated with treatment outcomes. Most AEs were either grade 1 or 2, and treatment-related grade 3 toxicities were observed in 8/25 (32%) patients.ConclusionCamrelizumab combined with XELOX plus bevacizumab or regorafenib was feasible, producing high rates of responses as first-line therapy in unselected Chinese patients with MSS mCRC. The toxicities were generally tolerable and manageable. Prospective randomized trials with large sample sizes are needed to evaluate these findings.

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“…Studies have revealed that TMB in dMMR/MSI-H CRCs is significantly higher than that in pMMR/MSI-L CRCs ( 48 , 67 – 69 ), and an increased amount of TMB in dMMR/MSI-H tumours can result in a 20-time higher rate of mutation and a stronger immune response than pMMR/MSI-L tumours ( 52 , 53 , 58 ), which are reflected in the very different composition and function of immune infiltrates in the TIME ( 70 – 73 ). Therefore, TMB appears to be an important biomarker for patients with dMMR/MSI-H CRC in response to anti-PD-1 therapy ( 68 , 74 – 77 ). Schrock et al.…”

Section: The Possible Mechanisms Leading To a Distinct Therapeutic Efmentioning

confidence: 99%

The Mechanisms Leading to Distinct Responses to PD-1/PD-L1 Blockades in Colorectal Cancers With Different MSI Statuses

Cui

2021

Front. Oncol.

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Current clinical studies showed distinct therapeutic outcomes, in which CRC patients with mismatch repair-deficient (dMMR)/microsatellite instability high (MSI-H) seem to be relatively more “sensitive” in response to anti-programmed death-1 receptor (PD-1)/programmed death-1 receptor ligand 1 (PD-L1) therapy than those with mismatch repair-proficient (pMMR)/microsatellite instability-low (MSI-L). The mechanisms by which the same PD-1/PD-L1 blockades lead to two distinct therapeutic responses in CRC patients with different MSI statuses remain poorly understood and become a topic of great interest in both basic research and clinical practice. In this review of the potential mechanisms for the distinct response to PD-1/PD-L1 blockades between dMMR/MSI-H CRCs and pMMR/MSI-L CRCs, relevant references were electronically searched and collected from databases PubMed, MEDLINE, and Google scholar. Sixty-eight articles with full text and 10 articles by reference-cross search were included for final analysis after eligibility selection according to the guidelines of PRISMA. Analysis revealed that multiple factors e.g. tumor mutation burden, immune cell densities and types in the tumor microenvironment, expression levels of PD-1/PD-L1 and cytokines are potential determinants of such distinct response to PD-1/PD-L1 blockades in CRC patients with different MSI statuses which might help clinicians to select candidates for anti-PD-1/PD-L1 therapy and improve therapeutic response in patients with CRC.

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Immunotherapy in Metastatic Colorectal Cancer: Could the Latest Developments Hold the Key to Improving Patient Survival?

Cited by 21 publications

References 91 publications

Radiomic signature of the FOWARC trial predicts pathological response to neoadjuvant treatment in rectal cancer

Radiomic signature of the FOWARC trial predicts pathological response to neoadjuvant treatment in rectal cancer

Preliminary Efficacy and Safety of Camrelizumab in Combination With XELOX Plus Bevacizumab or Regorafenib in Patients With Metastatic Colorectal Cancer: A Retrospective Study

The Mechanisms Leading to Distinct Responses to PD-1/PD-L1 Blockades in Colorectal Cancers With Different MSI Statuses

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