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Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement.

ABSTRACT: BACKGROUND:Colorectal cancer (CRC) tumor microenvironment (TME) characteristics, such as tumor infiltrating lymphocyte (TIL) densities and PD-L1 status, are predictive of recurrence, disease-free survival, and overall survival. In many malignancies, TME characteristics are also predictive of response to immunotherapy. As window of opportunity studies using neoadjuvant immunotherapy become more common and treatment guidelines incorporate TME features, accurate assessment of the pre-treatment TME using the biopsy specimen is critical. However, no study has thoroughly evaluated the correlation between the TMEs of the biopsy and resection specimens. METHODS:We conducted a retrospective analysis of patients with stage I-III CRC with matched biopsy and resection specimens. CD3+, CD4+, CD8+, and FoxP3+ lymphocyte populations at the center of tumor (CT) and invasive margin (IM) and tumor PD-L1 status in the biopsy and resection specimens were evaluated. TIL populations were compared using Mann-Whitney U tests or Student's t tests and correlated using Pearson r. RESULTS:CD3+ and CD4+ densities were significantly higher in the CT of the biopsy relative to the resection specimen Comparing biopsy and resection specimens, no TIL population at either the CT or IM had a correlation coefficient >?0.5. Determining PD-L1 status based on biopsy tissue resulted in a sensitivity of 37.1%, specificity of 81.4%, and accuracy of 61.5%. CONCLUSIONS:These findings demonstrate significant discordance between the TME of the biopsy and resection specimens. Caution should be used when basing treatment decisions on pre-treatment endoscopic biopsy findings and when interpreting changes in the TME between pre-treatment biopsy and resection specimens after neoadjuvant therapy.

SUBMITTER: Kemp Bohan PM

PROVIDER: S-EPMC7658304 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement.

Kemp Bohan Phillip M PM Chick Robert C RC Hickerson Annelies T AT Messersmith Lynn M LM Williams Grant M GM Cindass Jessica L JL Lombardo Jamie J Collins Ryan R Brady Robert O RO Hale Diane F DF Peoples George E GE Vreeland Timothy J TJ Clifton Guy T GT

Cancer immunology, immunotherapy : CII 20201112 5

<h4>Background</h4>Colorectal cancer (CRC) tumor microenvironment (TME) characteristics, such as tumor infiltrating lymphocyte (TIL) densities and PD-L1 status, are predictive of recurrence, disease-free survival, and overall survival. In many malignancies, TME characteristics are also predictive of response to immunotherapy. As window of opportunity studies using neoadjuvant immunotherapy become more common and treatment guidelines incorporate TME features, accurate assessment of the pre-treatm ...[more]

PMID: 33180182

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Project description:Background and study aims:?The majority of polyps removed at colonoscopy are diminutive (??5?mm) to small (<?10?mm) and there are few guidelines for the best way for these polyps to be removed. We aimed to assess the feasibility and effectiveness of cold biopsy forceps polypectomy with pre-lift (CBPP) for polyps ??7?mm. Our aims were to assess completeness of histological resection of this technique, to identify factors contributing to this and assess secondary considerations such as timing, retrieval and complication rates. Patients and methods?:We conducted a prospective cohort study on consecutive patients receiving a colonoscopy at Cheltenham General Hospital, as part of the National Bowel Cancer Screening Program (BCSP) in England. The study included only polyps that were judged as ??7?mm by the colonoscopist. A small sub-mucosal pre-lift injection was administered prior to removal of the polyp using cold biopsy forceps. One or more biopsies were taken until the polyp was confidently assessed visually as being completely removed by the colonoscopist. The entire polypectomy site was then removed en bloc by endomucosal resection (EMR) with a margin of at least 1 to 2?mm around defect. This was sent for histopathological analysis to assess completeness of resection. Polypectomy timing, tissue retrieval, number of bites required for visual resection and complications were recorded at the time of the procedure. Results?:Sixty-four patients were recruited and consented. Of them, 42 patients had a total of 60 polyps resected. Three patients had inflammatory polyps and were excluded from the study, leaving 57/60 polyps for final analysis. Seventeen were hyperplastic and 40 adenomatous polyps. Retrieval was complete for all 57 polyps and there were no complications both during or post- polypectomy. The complete resection rate (CRR) was 86?%. The technique was more effective in smaller polyps with 91.7?% of diminutive polyps (??5?mm) completely excised. Conclusions?:CBPP is a safe and highly effective technique for polyps <?5?mm with a high complete resection and retrieval rate. The time taken for the procedure is significantly greater than cold forceps alone, or cold snare as seen in other studies.

Project description:ImportanceA breast pathology diagnosis provides the basis for clinical treatment and management decisions; however, its accuracy is inadequately understood.ObjectivesTo quantify the magnitude of diagnostic disagreement among pathologists compared with a consensus panel reference diagnosis and to evaluate associated patient and pathologist characteristics.Design, setting, and participantsStudy of pathologists who interpret breast biopsies in clinical practices in 8 US states.ExposuresParticipants independently interpreted slides between November 2011 and May 2014 from test sets of 60 breast biopsies (240 total cases, 1 slide per case), including 23 cases of invasive breast cancer, 73 ductal carcinoma in situ (DCIS), 72 with atypical hyperplasia (atypia), and 72 benign cases without atypia. Participants were blinded to the interpretations of other study pathologists and consensus panel members. Among the 3 consensus panel members, unanimous agreement of their independent diagnoses was 75%, and concordance with the consensus-derived reference diagnoses was 90.3%.Main outcomes and measuresThe proportions of diagnoses overinterpreted and underinterpreted relative to the consensus-derived reference diagnoses were assessed.ResultsSixty-five percent of invited, responding pathologists were eligible and consented to participate. Of these, 91% (N = 115) completed the study, providing 6900 individual case diagnoses. Compared with the consensus-derived reference diagnosis, the overall concordance rate of diagnostic interpretations of participating pathologists was 75.3% (95% CI, 73.4%-77.0%; 5194 of 6900 interpretations). Among invasive carcinoma cases (663 interpretations), 96% (95% CI, 94%-97%) were concordant, and 4% (95% CI, 3%-6%) were underinterpreted; among DCIS cases (2097 interpretations), 84% (95% CI, 82%-86%) were concordant, 3% (95% CI, 2%-4%) were overinterpreted, and 13% (95% CI, 12%-15%) were underinterpreted; among atypia cases (2070 interpretations), 48% (95% CI, 44%-52%) were concordant, 17% (95% CI, 15%-21%) were overinterpreted, and 35% (95% CI, 31%-39%) were underinterpreted; and among benign cases without atypia (2070 interpretations), 87% (95% CI, 85%-89%) were concordant and 13% (95% CI, 11%-15%) were overinterpreted. Disagreement with the reference diagnosis was statistically significantly higher among biopsies from women with higher (n = 122) vs lower (n = 118) breast density on prior mammograms (overall concordance rate, 73% [95% CI, 71%-75%] for higher vs 77% [95% CI, 75%-80%] for lower, P < .001), and among pathologists who interpreted lower weekly case volumes (P < .001) or worked in smaller practices (P = .034) or nonacademic settings (P = .007).Conclusions and relevanceIn this study of pathologists, in which diagnostic interpretation was based on a single breast biopsy slide, overall agreement between the individual pathologists' interpretations and the expert consensus-derived reference diagnoses was 75.3%, with the highest level of concordance for invasive carcinoma and lower levels of concordance for DCIS and atypia. Further research is needed to understand the relationship of these findings with patient management.

Dataset Information

Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement.

Publications

Correlation of tumor microenvironment from biopsy and resection specimens in untreated colorectal cancer patients: a surprising lack of agreement.

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