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Density and distribution of lymphocytes in pretherapeutic rectal cancer and response to neoadjuvant therapy

ABSTRACT: Abstract

Background

Lymphocytic density in rectal cancer has been reported to be associated with therapeutic response, but the role of the lymphocytic distribution pattern remains to be determined. This study aimed to evaluate the association between the distribution and density of lymphocytes in rectal-cancer tissue with tumor response to neoadjuvant therapy.

Methods

We retrospectively analysed 134 patients with rectal cancer receiving neoadjuvant therapy within a prospectively maintained cohort. Pretherapeutic biopsy samples were stained with immunohistochemistry (CD4 and CD8). Densities of intratumoral periglandular lymphocytes (IPLs) and tumor-infiltrating lymphocytes (TILs) were assessed separately. Logistic-regression analysis was used to assess associations of lymphocyte densities with tumor regression grade (TRG), controlling for clinicopathological, molecular, and regimen features.

Results

Compared with cases in the lowest quartile of CD8+ TILs, those in the highest quartile were significantly associated with better TRG (multivariate odds ratio, 0.23; 95% confidence interval, 0.07 to 0.76; P?Conclusions Our data suggest that CD8+ TILs, but not IPLs, are independently associated with response to neoadjuvant therapy, regardless of the regimen of radiation or chemotherapy.

SUBMITTER: Lai S

PROVIDER: S-EPMC7793145 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Project description:ObjectivesA watch and wait strategy with the goal of organ preservation is an emerging treatment paradigm for rectal cancer following neoadjuvant treatment. However, the selection of appropriate patients remains a challenge. Most previous efforts to measure the accuracy of MRI in assessing rectal cancer response used a small number of radiologists and did not report variability among them.MethodsTwelve radiologists from 8 institutions assessed baseline and restaging MRI scans of 39 patients. The participating radiologists were asked to assess MRI features and to categorize the overall response as complete or incomplete. The reference standard was pathological complete response or a sustained clinical response for > 2 years.ResultsWe measured the accuracy and described the interobserver variability of interpretation of rectal cancer response between radiologists at different medical centers. Overall accuracy was 64%, with a sensitivity of 65% for detecting complete response and specificity of 63% for detecting residual tumor. Interpretation of the overall response was more accurate than the interpretation of any individual feature. Variability of interpretation was dependent on the patient and imaging feature investigated. In general, variability and accuracy were inversely correlated.ConclusionsMRI-based evaluation of response at restaging is insufficiently accurate and has substantial variability of interpretation. Although some patients' response to neoadjuvant treatment on MRI may be easily recognizable, as seen by high accuracy and low variability, that is not the case for most patients.Key points• The overall accuracy of MRI-based response assessment is low and radiologists differed in their interpretation of key imaging features. • Some patients' scans were interpreted with high accuracy and low variability, suggesting that these patients' pattern of response is easier to interpret. • The most accurate assessments were those of the overall response, which took into consideration both T2W and DWI sequences and the assessment of both the primary tumor and the lymph nodes.

Project description:Purpose To investigate the value of T2-weighted-based radiomics compared with qualitative assessment at T2-weighted imaging and diffusion-weighted (DW) imaging for diagnosis of clinical complete response in patients with rectal cancer after neoadjuvant chemotherapy-radiation therapy (CRT). Materials and Methods This retrospective study included 114 patients with rectal cancer who underwent magnetic resonance (MR) imaging after CRT between March 2012 and February 2016. Median age among women (47 of 114, 41%) was 55.9 years (interquartile range, 45.4-66.7 years) and median age among men (67 of 114, 59%) was 55 years (interquartile range, 48-67 years). Surgical histopathologic analysis was the reference standard for pathologic complete response (pCR). For qualitative assessment, two radiologists reached a consensus. For radiomics, one radiologist segmented the volume of interest on high-spatial-resolution T2-weighted images. A random forest classifier was trained to separate the patients by their outcomes after balancing the number of patients in each response category by using the synthetic minority oversampling technique. Statistical analysis was performed by using the Wilcoxon rank-sum test, McNemar test, and Benjamini-Hochberg method. Results Twenty-one of 114 patients (18%) achieved pCR. The radiomic classifier demonstrated an area under the curve of 0.93 (95% confidence interval [CI]: 0.87, 0.96), sensitivity of 100% (95% CI: 0.84, 1), specificity of 91% (95% CI: 0.84, 0.96), positive predictive value of 72% (95% CI: 0.53, 0.87), and negative predictive value of 100% (95% CI: 0.96, 1). The diagnostic performance of radiomics was significantly higher than was qualitative assessment at T2-weighted imaging or DW imaging alone (P < .02). The specificity and positive predictive values were significantly higher in radiomics than were at combined T2-weighted and DW imaging (P < .0001). Conclusion T2-weighted-based radiomics showed better classification performance compared with qualitative assessment at T2-weighted and DW imaging for diagnosing pCR in patients with locally advanced rectal cancer after CRT. © RSNA, 2018 Online supplemental material is available for this article.