The potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer

Jäger, Tarkan; Neureiter, Daniel; Fallaha, Mohammad; Schredl, Philipp; Kiesslich, Tobias; Urbas, Romana; Klieser, E.; Holzinger, Josef; Sedlmayer, Felix; Emmanuel, Klaus; Dinnewitzer, Adam

doi:10.1007/s00066-018-1340-0

Cited by 18 publications

(20 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of the most recent studies, Jäger et al [3] can be compared to our own study. As in our study, they evaluated budding not only at the invasive front but also throughout the tumor.…”

Section: Discussionmentioning

confidence: 95%

“…Budding has been described as a prognostic feature after chemoradiotherapy in rectal cancer patients in several publications with the general limitation of a retrospective study design. In previous studies, budding was reported in 10.1-63.2% of cases due to different methodologies used for evaluation [3,[15][16][17][18][19][20]. Budding has been shown to be a negative prognostic factor for survival in different kinds of study designs and for a broad range of cut-offs.…”

Section: Discussionmentioning

confidence: 99%

“…The tumor, node, metastasis (TNM) staging system, which is continuously updated, is widely used to predict outcomes and aids in clinical decision making in colorectal cancer. However, after preoperative therapy, the prognostic impact of the classical TNM system is subject to certain limitations, especially in tumors with wide fibrotic areas, i.e., a major therapeutic response [3]. Furthermore, the assessment of tumor regression, the relation of residual cancer cells to fibrosis, is an important feature of pathohistological evaluation protocols of rectal cancer after neoadjuvant therapy.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

et al. 2019

View full text Add to dashboard Cite

Background: Budding is a complementary prognostic factor for colorectal cancer. In this study, we aimed to clarify the role of tumor budding in rectal cancer patients after preoperative chemoradiotherapy. Methods: A total of 124 patients with rectal cancer treated with neoadjuvant chemoradiotherapy and consecutive surgery were included. Surgical specimens were evaluated for budding and routine clinicopathological features. Budding was evaluated on hematoxylin and eosin (H&E)-stained slides and by cytokeratin immunohistochemical (IHC) staining. Results: A budding rate of 36.9% (n = 38) by H&E and 55.6% (n = 55) by IHC was observed. Budding was significantly associated with a high ypT and ypN status, poor differentiation, and low degrees of tumor regression. Moreover, budding was strongly predictive of a worse patient outcome, as measured by tumor recurrence or death. In multivariate analyses, budding remained the only significant parameter for overall survival and was even superior to the ypT and ypN status (budding in H&E: hazard ratio (HR) 2.72, 95% confidence interval (95% CI) 1.15-6.44, p = 0.023; budding in IHC: HR 5.19, 95% CI 1.62-16.61, p = 0.006). Conclusion: Budding is a strong prognostic predictor of survival in rectal cancer patients after neoadjuvant therapy. A standardized evaluation of tumor budding after neoadjuvant therapy may thus aid in risk stratification and guide the clinical management of patients with rectal cancer. Immunostaining can help to enhance the diagnostic accuracy and prognostic significance.

show abstract

“…Of the most recent studies, Jäger et al [3] can be compared to our own study. As in our study, they evaluated budding not only at the invasive front but also throughout the tumor.…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

et al. 2019

View full text Add to dashboard Cite

show abstract

“…It was an independent marker for dramatically worse overall survival in rectal cancer patients. Prognostic markers are important for accurately individualizing therapies for rectal cancer patients, thereby reducing long-term costs and patient suffering [ 48 , 49 ]. Given the strong prognostic significance in this investigation for rectal cancer patients, additional studies on cell-in-cell structures and senescence are clearly warranted.…”

Section: Discussionmentioning

confidence: 99%

Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

Gottwald

Putz

Hohmann

et al. 2020

BMC Mol and Cell Biol

View full text Add to dashboard Cite

Background Non-professional phagocytosis is usually triggered by stimuli such as necrotic cell death. In tumor therapy, the tumors often disappear slowly and only long time after the end of therapy. Here, tumor therapy inactivates the cells by inducing senescence. Therefore, study focused whether senescence is a stimulus for non-professional phagocytosis or whether senescent cells themselves phagocytize non-professionally. Results Senescence was induced in cell lines by camptothecin and a phagocytosis assay was performed. In tissue of a cohort of 192 rectal cancer patients senescence and non-professional phagocytosis was studied by anti-histone H3K9me3 and anti-E-cadherin staining. Senescent fibroblasts and pancreas carcinoma cells phagocytize necrotic cells but are not phagocytized. In the tissue of rectal carcinoma, senescent cells can phagocytize and can be phagocytized. A high number of senescent cells and, at the same time, high numbers of non-professional phagocytizing cells in the rectal carcinoma tissue lead to an extremely unfavorable prognosis regarding overall survival. Conclusion Senescent cells can be non-professionally phagocytized and at the same time they can non-professionally phagocytize in vivo. In vitro experiments indicate that it is unlikely that senescence is a strong trigger for non-professional phagocytosis. Combined high rates of non-professional phagocytosis and high rates of senescence are an extremely poor prognostic factor for overall survival.

show abstract

“…All patients received neoadjuvant radiochemotherapy treatment including 50.4 Gy overall dose fractured into 28 sessions of 1.8 Gy and chemotherapy including 5-FU for an overall period of 38 days. 10,11 The tumor response was surveilled 8 weeks post-RCT with proctoscopy, CT of the pelvis, endorectal ultrasound and clinical examination. Thereafter, tumor resection was performed in 191 patients.…”

Section: Treatment Protocolmentioning

confidence: 99%

Regulatory T cells and cytotoxic T cells close to the epithelial–stromal interface are associated with a favorable prognosis

et al. 2020

View full text Add to dashboard Cite

Cytotoxic T cells and regulatory T cells play a crucial role in the outcome of cancer patients. Besides the density of these cells, it was shown recently that the spatial distribution is equally important. Here, we specifically analyzed the spatial distribution of these T cell subtypes at the epithelial-stromal interface in a rectal cancer cohort and its relevance for prognosis. We studied a cohort of 191 patients with advanced rectal cancer treated by radiochemotherapy (RCT). Tissue microarrays were immunohistochemical double-stained by FoxP3+ and CD+. Cell densities were analyzed in the stromal and epithelial compartment. Additionally, an image analysis software calculated the distances of lymphocytes to the epithelial-stromal interface (ESI). CD8+ and FoxP3+ cell counts decreased clearly after RCT with the decrease of FoxP3+ being more pronounced than of CD8+ cells. In the invasive front, short distances of the ESI to CD8+ and to FoxP3+ cells were associated with improved overall survival. Cell counts in the stromal compartment had no influence on prognosis. No correlation between stromal and epithelial lymphocyte densities was observed. The distance of epithelial-stromal interface to CD8+ and FoxP3+ cells was more accurate in predicting prognosis in the stromal compartment of rectal cancer patients than mere cell counts and could thereby be means of better stratifying patients for therapy. This observation will have to be validated in future prospective studies with regard to other tumor entities and its implications for the responsiveness of tumors to new therapeutic modalities.

show abstract

The potential predictive value of tumor budding for neoadjuvant chemoradiotherapy response in locally advanced rectal cancer

Cited by 18 publications

References 65 publications

Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

Tumor budding outperforms ypT and ypN classification in predicting outcome of rectal cancer after neoadjuvant chemoradiotherapy

Role of tumor cell senescence in non-professional phagocytosis and cell-in-cell structure formation

Regulatory T cells and cytotoxic T cells close to the epithelial–stromal interface are associated with a favorable prognosis

Contact Info

Product

Resources

About