Intratumoral budding and automated CD8-positive T-cell density in pretreatment biopsies can predict response to neoadjuvant therapy in rectal adenocarcinoma

Farchoukh, Lama; Hartman, Douglas J.; Ma, Changqing; Celebrezze, James; Medich, David S.; Bahary, Nathan; Frank, Madison; Pantanowitz, Liron; Pai, Reetesh K.

doi:10.1038/s41379-020-0619-8

Cited by 23 publications

(35 citation statements)

References 32 publications

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“…The Spatial Immuno-Oncology Index, 30,31 which integrates tumor budding and lymphocytic infiltration within 50 mm of the tumor buds with the ratio of CD68 þ /CD163 þ macrophages, was able to stratify stage II colorectal cancer and outperformed previous scores that incorporated tumor budding, immunoscore, and pT stage metrics. Farchoukh et al 37 reported CD8 þ T-cell density by DIA and intratumoral budding by visual assessment in pretreatment biopsies of rectal adenocarcinoma as independent predictive biomarkers of response to neoadjuvant therapy. Nestarenkaite at al 25 proposed a prognostic Immuno-Interface Score for colorectal cancer survival probability based on independent contributions of CD8 and CD20 immunogradients along with the invasive growth pattern determined by pathologists' visual assessment; this approach outperformed evaluation of tumor budding alone.…”

Section: Tumor-stroma Architecturementioning

confidence: 99%

Machine-Learning–Based Evaluation of Intratumoral Heterogeneity and Tumor-Stroma Interface for Clinical Guidance

Laurinavičius

Rasmusson

Plancoulaine

et al. 2021

The American Journal of Pathology

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Section: Tumor-stroma Architecturementioning

confidence: 99%

Machine-Learning–Based Evaluation of Intratumoral Heterogeneity and Tumor-Stroma Interface for Clinical Guidance

Laurinavičius

Rasmusson

Plancoulaine

et al. 2021

The American Journal of Pathology

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“…Recently, NT has emerged as the standard treatment for LARC patients[ 11 - 14 ]. Patients who cannot achieve a pCR usually undergo surgery and receive adjuvant therapy.…”

Section: Discussionmentioning

confidence: 99%

“…A lower probability of recurrence leads to a higher survival rate. In previous studies, recurrence has been linked with biomarkers such as BRAF-6000E, RAS and CD8-positive T-cells[ 11 , 34 , 35 ], and an early diagnosis[ 25 ] can take advantage of the patients’ clinical information. In identifying predictive factors of DFS, 50 clinical features were reduced to 2 potential predictors of DFS.…”

Section: Discussionmentioning

confidence: 99%

Nomograms and risk score models for predicting survival in rectal cancer patients with neoadjuvant therapy

Wei¹,

Mei²,

Chen³

et al. 2020

WJG

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BACKGROUND Colorectal cancer is a common digestive cancer worldwide. As a comprehensive treatment for locally advanced rectal cancer (LARC), neoadjuvant therapy (NT) has been increasingly used as the standard treatment for clinical stage II/III rectal cancer. However, few patients achieve a complete pathological response, and most patients require surgical resection and adjuvant therapy. Therefore, identifying risk factors and developing accurate models to predict the prognosis of LARC patients are of great clinical significance. AIM To establish effective prognostic nomograms and risk score prediction models to predict overall survival (OS) and disease-free survival (DFS) for LARC treated with NT. METHODS Nomograms and risk factor score prediction models were based on patients who received NT at the Cancer Hospital from 2015 to 2017. The least absolute shrinkage and selection operator regression model were utilized to screen for prognostic risk factors, which were validated by the Cox regression method. Assessment of the performance of the two prediction models was conducted using receiver operating characteristic curves, and that of the two nomograms was conducted by calculating the concordance index (C-index) and calibration curves. The results were validated in a cohort of 65 patients from 2015 to 2017. RESULTS Seven features were significantly associated with OS and were included in the OS prediction nomogram and prediction model: Vascular_tumors_bolt, cancer nodules, yN, body mass index, matchmouth distance from the edge, nerve aggression and postoperative carcinoembryonic antigen. The nomogram showed good predictive value for OS, with a C-index of 0.91 (95%CI: 0.85, 0.97) and good calibration. In the validation cohort, the C-index was 0.69 (95%CI: 0.53, 0.84). The risk factor prediction model showed good predictive value. The areas under the curve for 3- and 5-year survival were 0.811 and 0.782. The nomogram for predicting DFS included ypTNM and nerve aggression and showed good calibration and a C-index of 0.77 (95%CI: 0.69, 0.85). In the validation cohort, the C-index was 0.71 (95%CI: 0.61, 0.81). The prediction model for DFS also had good predictive value, with an AUC for 3-year survival of 0.784 and an AUC for 5-year survival of 0.754. CONCLUSION We established accurate nomograms and prediction models for predicting OS and DFS in patients with LARC after undergoing NT.

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“…Patients diagnosed with primary invasive rectal adenocarcinoma on pretreatment biopsy accessioned at the Department of Pathology, University of Pittsburgh Medical Center from 2010 to 2019 were retrospectively identified by review of an institutional database, and have been previously analysed by our group. 9 Patients with locally advanced rectal adenocarcinoma involving the mid-or distal rectum and who underwent neoadjuvant therapy were included. Patients without available pretreatment tumour biopsy for analysis or with distant metastases at the time of diagnosis were excluded.…”

Section: Methodsmentioning

confidence: 99%

“…Recently, our group demonstrated that CD8 + T cell density and intratumoral budding (ITB) in pretreatment biopsies of rectal adenocarcinoma were independent predictive biomarkers of response to neoadjuvant therapy. 9 However, the relationship of TP53 with the above two predictive factors has not been investigated. In this study, we evaluated the predictive and prognostic value of TP53 for therapy response and disease-free survival in rectal cancer, as well as its interaction with CD8 + T cell density and ITB.…”

Section: Introductionmentioning

confidence: 99%

Combined histopathological risk score using TP53 protein expression, CD8⁺ T cell density and intratumoral budding is an independent predictor of neoadjuvant therapy response in rectal adenocarcinoma

et al. 2021

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Combined histopathological risk score using TP53 protein expression, CD8 + T cell density and intratumoral budding is an independent predictor of neoadjuvant therapy response in rectal adenocarcinomaAims: Neoadjuvant therapy is the recommended treatment for locally advanced rectal adenocarcinoma; however, there remains significant variability in response to therapy. Tumour protein 53 (TP53) has been associated with therapy response and prognosis with conflicting data. Recently, we demonstrated that immune cell density and intratumoral budding (ITB) are predictive factors in rectal cancer. We investigated the predictive value of TP53 immunohistochemistry with CD8 + T cell density and ITB on pretreatment biopsies of rectal adenocarcinoma for response to neoadjuvant therapy. Methods and results: Pretreatment biopsies of rectal adenocarcinoma from 117 patients with neoadjuvant therapy were analysed for TP53 expression by immunohistochemistry, ITB, CD8 + T cell density and mismatch repair protein (MMR) status. Most rectal adenocarcinomas displayed aberrant TP53 expression (86 of 117, 74%). Compared to wild-type TP53, aberrant TP53 expression was associated with proficient MMR status (P = 0.003) and low CD8 + T cell density (P = 0.001). Aberrant TP53 was significantly associated with a partial to poor response to neoadjuvant therapy [odds ratio (OR) = 2.42, 95% confidence interval (CI) = 1.04-5.62, P = 0.04]. A combined histopathological risk score (HRS) was created using CD8 + T cell density, ITB and TP53 expression. Patients were separated into low (none to one factor) and high (two to three factors) HRS categories. In the multivariable model, patients with a high HRS were 3.25-fold more likely to have a partial or poor response to neoadjuvant therapy (95% CI = 1.48-7.11, P = 0.003). Conclusions: Our study demonstrates that aberrant TP53 expression, high ITB and low CD8 + T cell density in pretreatment biopsies can help predict response to neoadjuvant therapy. These biomarkers may be helpful in identifying patients at risk for therapy resistance.

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Intratumoral budding and automated CD8-positive T-cell density in pretreatment biopsies can predict response to neoadjuvant therapy in rectal adenocarcinoma

Cited by 23 publications

References 32 publications

Machine-Learning–Based Evaluation of Intratumoral Heterogeneity and Tumor-Stroma Interface for Clinical Guidance

Machine-Learning–Based Evaluation of Intratumoral Heterogeneity and Tumor-Stroma Interface for Clinical Guidance

Nomograms and risk score models for predicting survival in rectal cancer patients with neoadjuvant therapy

Combined histopathological risk score using TP53 protein expression, CD8⁺ T cell density and intratumoral budding is an independent predictor of neoadjuvant therapy response in rectal adenocarcinoma

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Intratumoral budding and automated CD8-positive T-cell density in pretreatment biopsies can predict response to neoadjuvant therapy in rectal adenocarcinoma

Cited by 23 publications

References 32 publications

Machine-Learning–Based Evaluation of Intratumoral Heterogeneity and Tumor-Stroma Interface for Clinical Guidance

Machine-Learning–Based Evaluation of Intratumoral Heterogeneity and Tumor-Stroma Interface for Clinical Guidance

Nomograms and risk score models for predicting survival in rectal cancer patients with neoadjuvant therapy

Combined histopathological risk score using TP53 protein expression, CD8+ T cell density and intratumoral budding is an independent predictor of neoadjuvant therapy response in rectal adenocarcinoma

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Combined histopathological risk score using TP53 protein expression, CD8⁺ T cell density and intratumoral budding is an independent predictor of neoadjuvant therapy response in rectal adenocarcinoma