Tumor Regression Grading After Preoperative Chemoradiotherapy for Locally Advanced Rectal Carcinoma Revisited: Updated Results of the CAO/ARO/AIO-94 Trial

Purpose We previously described the prognostic impact of tumor regression grading (TRG) on the outcome of patients with rectal carcinoma treated with preoperative chemoradiotherapy (CRT) in the CAO/ARO/AIO-94 trial. Here we report long-term results after a median follow-up of 132 months. Patients and Methods TRG after preoperative CRT was determined in 386 surgical specimens by the amount of viable tumor cells versus fibrosis, ranging from TRG 4 (no viable tumor cells) to TRG 0 (no signs of regression). Clinicopathologic parameters and TRG were correlated to the cumulative incidence of local recurrence, distant metastasis, and disease-free survival (DFS). Results Ten-year cumulative incidence of distant metastasis and DFS were 10.5% and 89.5% for patients with TRG 4 (complete regression), 29.3% and 73.6% for TRG 2 and 3 (intermediate regression), and 39.6% and 63% for TRG 0 and 1 (poor regression), respectively (P = .005 and P = .008, respectively). On multivariable analysis, residual lymph node metastasis (ypN+) and TRG were the only independent prognostic factors for cumulative incidence of distant metastasis (P < .001 and P = .035, respectively) and DFS (P < .001 and P = .039, respectively), whereas local recurrence was significantly affected by ypN status (P < .001) and lymphatic invasion (P = .026). Conclusion Complete and intermediate tumor regressions were associated with improved long-term outcome in patients with rectal carcinoma after preoperative CRT independent of clinicopathologic parameters. This classification system needs to be prospectively tested in multiple data sets to validate its reproducibility in a wider setting.

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Search of Predictors of Radiosensitivity in Rectal Adenocarcinoma

Medical Radiology and radiation safety ◽

10.12737/1024-6177-2021-66-5-39-44 ◽

2021 ◽

Vol 66 (5) ◽

pp. 39-44

Author(s):

M. Vologirova ◽

N. Volchenko ◽

I. Zamulaeva ◽

I. Droshneva ◽

A. Boyko ◽

...

Keyword(s):

Tumor Cells ◽

Tumor Regression ◽

Rectal Adenocarcinoma ◽

Treatment Method ◽

Clinical Situation ◽

Preoperative Chemoradiotherapy ◽

Fourth Degree ◽

Immunohistochemical Markers ◽

Degree Of Differentiation ◽

E Cadherin

Purpose: To analyze a number of immunohistochemical markers as predictors of the radiosensitivity of rectal adenocarcinoma. Material and methods: The study included 122 patients with histologically verified rectal adenocarcinoma, varying degrees of differentiation, and the stage of the tumor process I-IIIC, T2-T4b /N0-N2b/ M0, with the localization of the tumor in the lower-middle-ampullary parts of the rectum. Predictors included in the research: Ki67, p53, EGFR, Bcl2, COX2, P21, E-cadherin. Preoperative chemoradiotherapy was performed up to 48–50 Gy with the use of medications (5-FU, Cisplatin) as a radio modifiers. The analysis was carried out according to the degree of severity of therapeutic pathomorphosis (according to Mandard), a decrease in the stage before surgery. Results: A full course of preoperative chemoradiotherapy followed by surgery was performed at 121 patients, one patient died of concomitant cardiac pathology during the break. The first degree of Mandard pathomorphosis (complete resorption) registered at 12 patients. The second degree (preservation of a few tumor cells against the background of fibrotic changes) – at 27 patients. The third degree (a large number of preserved tumor cells against the background of the predominance of fibrosis) – at 38 patients. The fourth degree (tumor cells predominate over fibrotic changes) – at 27 patients. The fifth degree (complete absence of signs of tumor regression, absence of fibrosis) – at 2 patients. A decrease in the stage of the tumor process according to the preoperative comprehensive examination registered in 114 (94.2%) patients, in 9 (7.4%) patients – there was no dynamics. During the observation period from 2006 until nowadays, 10 people are known to have died. Years in remission range from 3 months to 22 years. According to the results of multivariate and multiple regression analyses, it is possible to successfully predict the effectiveness of chemoradiotherapy, both with the use of biomarkers (Ki67, p53, EGFR, Bcl2, COX2, P21, E-cadherin), and traditional indicators (histological type, stage of the disease, gender, degree of differentiation). It turned out, that both traditional indicators and immunohistochemical indicators work equally well, regardless of each other. Conclusion: Studied immunohistochemical predictors of radiosensitivity of rectal adenocarcinoma, allow to assess the degree of radiosensitivity or radioresistance of the tumor in each patient before the start of preoperative chemoradiotherapy by doing so, it warns us about the effectiveness or ineffectiveness of chemoradiotherapy in a specific clinical situation, which allows us to individualize the approach to treatment, choosing a more suitable treatment method for the patient: neoadjuvant chemotherapy or surgery.

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Tumor Regression Grading After Preoperative Chemoradiotherapy as a Prognostic Factor and Individual-Level Surrogate for Disease-Free Survival in Rectal Cancer

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djx095 ◽

2017 ◽

Vol 109 (12) ◽

Cited By ~ 35

Author(s):

Emmanouil Fokas ◽

Philipp Ströbel ◽

Rainer Fietkau ◽

Michael Ghadimi ◽

Torsten Liersch ◽

...

Keyword(s):

Rectal Cancer ◽

Prognostic Factor ◽

Tumor Regression ◽

Disease Free Survival ◽

Preoperative Chemoradiotherapy ◽

Free Survival ◽

Individual Level ◽

Regression Grading ◽

Disease Free

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Comparison of long-term survival outcomes between laparoscopic and open surgery for mid or low rectal cancer treated with preoperative chemoradiotherapy: 7-year follow-up of COREAN trial.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.3518 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 3518-3518

Author(s):

Ji Won Park ◽

Seung-Yong Jeong ◽

Sung-Bum Kang ◽

Jungnam Joo ◽

Mi Kyung Song ◽

...

Keyword(s):

Rectal Cancer ◽

Laparoscopic Surgery ◽

Local Recurrence ◽

Open Surgery ◽

Disease Free Survival ◽

Preoperative Chemoradiotherapy ◽

Low Rectal Cancer ◽

Free Survival ◽

Disease Free

3518 Background: Laparoscopic surgery for rectal cancer has been used widely. However, recent two randomized trials raised concerns about short-term oncologic safety of laparoscopic surgery for rectal cancer. The aim of this study was to evaluate the long-term oncologic safety of laparoscopic surgery for rectal cancer based on 7-year data from the Comparison of Open versus laparoscopic surgery for mid or low REctal cancer After Neoadjuvant chemoradiotherapy (COREAN) trial. Methods: COREAN trial was a non-inferiority, randomized controlled trial. Between April, 2006, and Aug, 2009, eligible participants with mid or low rectal cancer treated with preoperative chemoradiotherapy were randomly assigned (1:1) to laparoscopic (n = 170) or open surgery (n = 170). Seven-year outcomes included overall and disease-free survival, and local recurrence. Log-rank test and stratified Cox regression analysis were used for survival analysis. Analysis was by intention to treat. Results: The median follow-up times were 84 months (IQR: 61.5-97.0). No differences were found between laparoscopic and open surgery group in terms of overall and disease-free survival, and local recurrence (7-year overall survival: 83.2% [laparoscopic] vs 77.3% [open], p = 0.48; 7-year disease-free survival: 71.6% [laparoscopic] vs 64.3% [open], p = 0.20; 7-year local recurrence: 3.3% [laparoscopic] vs 7.9% [open], p = 0.08). Stratified Cox regression analysis adjusted for ypT, ypN and tumor regression grade showed no significant difference between groups in terms of overall and disease-free survival, and local recurrence. The hazard ratios for overall survival, disease-free survival and local recurrence (open vs laparoscopic surgery) were 0.96 (95% CI = 0.58-1.57), 1.03 (95% CI = 0.70-1.53), and 2.28 (95% CI = 0.82-7.16), respectively. Conclusions: The 7-year analysis confirm the long-term oncological safety of laparoscopic surgery for rectal cancer treated with preoperative chemoradiotherapy. The use of laparoscopic surgery does not compromise the long-term survival outcomes in rectal cancer. Clinical trial information: NCT00470951.

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Tumor regression grading after neoadjuvant chemotherapy predicts long-term outcome of stage IIIC epithelial ovarian cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.5547 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. 5547-5547

Author(s):

Mingyi Zhou ◽

Liankun Li ◽

Xiaobin Wang ◽

Chunyan Wang ◽

Danbo Wang

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Tumor Regression ◽

Stage Iiic ◽

Term Outcome ◽

Long Term Outcome ◽

Regression Grading

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Pathological Assessment of the AJCC Tumor Regression Grading System After Preoperative Chemoradiotherapy for Chinese Locally Advanced Rectal Cancer

Medicine ◽

10.1097/md.0000000000002272 ◽

2016 ◽

Vol 95 (3) ◽

pp. e2272 ◽

Cited By ~ 5

Author(s):

Lu-Ning Zhang ◽

Wei-Wei Xiao ◽

Shao-Yan Xi ◽

Pu-Yun OuYang ◽

Kai-Yun You ◽

...

Keyword(s):

Rectal Cancer ◽

Tumor Regression ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Preoperative Chemoradiotherapy ◽

Locally Advanced Rectal Cancer ◽

Grading System ◽

Regression Grading ◽

Pathological Assessment

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Improving efficacy of PD-1 blockade in unresponsive lymphoma tumors with in situ vaccination through induction of a highly efficient cross-presenting dendritic cell subset.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.5_suppl.76 ◽

2018 ◽

Vol 36 (5_suppl) ◽

pp. 76-76

Author(s):

Linda Hammerich ◽

Maxime Dhainaut ◽

Thomas A. Davis ◽

Tibor Keler ◽

Andres M. Salazar ◽

...

Keyword(s):

T Cells ◽

Tumor Cells ◽

Cd8 T Cells ◽

Tumor Regression ◽

Low Grade ◽

Dendritic Cell Subset ◽

Term Survival ◽

Intratumoral Injections

76 Background: Low-grade non-Hodgkin’s B-cell lymphomas are generally incurable; preliminary results with anti-PD-1 therapy have yielded low response rates. Tumoral DC infiltration correlates with efficacy of checkpoint blockade and tumor-targeted vaccines represent promising, novel treatment strategies to induce anti-tumor T cells. Methods: A20 lymphoma-bearing mice were treated with a PD-1 blocking antibody with an in situ vaccine (ISV) consisting of intratumoral injections of FMS-like tyrosine kinase-3 ligand (Flt3L), local irradiation (XRT) of the tumor and intratumoral injections of the TLR3 agonist poly-ICLC (pIC). Results: Untreated lymphoma tumors contained very low numbers of DC and treatment with anti-PD1 alone did not induce tumor regression or increase survival. Flt3L treatment resulted in a dramatic increase of IRF8+TLR3+ DC at the tumor site, the draining lymph node and the spleen. XRT of A20 cells induced activation of Flt3L-treated splenic DC in vitro and local XRT of the tumor in vivo induced expression of CD103 on infiltrating TLR3+ DC. Local XRT also enhanced uptake of dying tumor cells by DC. Interestingly, tumor antigens were taken up mainly by CD103+ DC and not CD103- subtypes. CD103+ expression distinguishes a subset of migratory cross-presenting DC. Accordingly, CD103+ DC isolated from the tumor induced proliferation of tumor-specific CD8+ T cells more efficiently than CD103- subsets. The combination of Flt3L with XRT and pIC induced tumor-reactive, IFNg-producing T cells, but delayed tumor growth and improved survival only in 40% of mice. ISV also increased expression of PD-L1 on tumor cells and tumor infiltrating DC. Consistently, combination of ISV with PD-1 blockade led to complete tumor regression and increased long-term survival in the majority of mice. PD-1 blockade also increased the number of tumor-reactive T cells and depletion of CD8+ T cells abrogated the anti-tumor effect. Conclusions: In situ vaccination can improve efficacy of anti-PD-1 in checkpoint-unresponsive lymphoma tumors through induction of a cross-presenting DC subset leading to long-term regression of established lymphoma tumors.

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The influence of the distal resection margin length on local recurrence and long- term survival in patients with rectal cancer after chemoradiotherapy and sphincter- preserving rectal resection

Radiology and Oncology ◽

10.1515/raon-2016-0030 ◽

2017 ◽

Vol 51 (2) ◽

pp. 169-177 ◽

Cited By ~ 3

Author(s):

Jan Grosek ◽

Vaneja Velenik ◽

Ibrahim Edhemovic ◽

Mirko Omejc

Keyword(s):

Rectal Cancer ◽

Local Recurrence ◽

Resection Margin ◽

Preoperative Chemoradiotherapy ◽

Distal Resection Margin ◽

Term Survival ◽

Long Term Survival ◽

Group Iii ◽

Group I

Abstract Background Low recurrence rates and long term survival are the main therapeutic goals of rectal cancer surgery. Complete, margin- negative resection confers the greatest chance for a cure. The aim of our study was to determine whether the length of the distal resection margin was associated with local recurrence rate and long- term survival. Patients and methods One hundred and nine patients, who underwent sphincter-preserving resection for locally advanced rectal cancer after preoperative chemoradiotherapy between 2006 and 2010 in two tertiary referral centres were included in the study. Distal resection margin lengths were measured on formalin-fixed, pinned specimens. Characteristics of patients with distal resection margin < 8 mm (Group I, n = 27), 8–20 mm (Group II, n = 31) and > 20 mm (Group III, n = 51) were retrospectively analysed and compared. Median (range) follow-up time in Group I was 89 (51–111), in Group II 83 (57–111) and in Group III 80 (45–116) months (p = 0.326), respectively. Results Univariate survival analysis showed that distal resection margin length was not statistically significantly associated with overall survival or local recurrence rate (p > 0.05). In a multiple Cox regression analysis, after adjusting for pathologic T and N stage (yT, yN), distal resection margin length was still not statistically significantly associated with overall survival. Conclusions Our study shows that close distal resection margins can be accepted as oncologically safe for sphincter-preserving rectal resections after preoperative chemoradiotherapy.

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Influence of Body Mass Index on Long-Term Outcome in Patients with Rectal Cancer—A Single Centre Experience

Cancers ◽

10.3390/cancers11050609 ◽

2019 ◽

Vol 11 (5) ◽

pp. 609 ◽

Cited By ~ 3

Author(s):

Kalb ◽

Langheinrich ◽

Merkel ◽

Krautz ◽

Brunner ◽

...

Keyword(s):

Body Mass Index ◽

Rectal Cancer ◽

Overall Survival ◽

Local Recurrence ◽

Distant Metastasis ◽

Hazard Ratio ◽

Term Outcome ◽

Long Term Outcome ◽

Obesity Class

Background: Excess bodyweight is known to influence the risk of colorectal cancer; however, little evidence exists for the influence of the body mass index (BMI) on the long-term outcome of patients with rectal cancer. Methods: We assessed the impact of the BMI on the risk of local recurrence, distant metastasis and overall—survival in 612 patients between 2003 and 2010 after rectal cancer diagnosis and treatment at the University Hospital Erlangen. A Cox-regression model was used to estimate the hazard ratio and multivariate risk of mortality and distant-metastasis. Median follow up-time was 58 months. Results: Patients with obesity class II or higher (BMI ≥ 35 kg/m2, n = 25) and patients with underweight (BMI < 18.5 kg/m2, n = 5) had reduced overall survival (hazard ratio (HR) = 1.6; 95% confidence interval (CI) 0.9–2.7) as well as higher rates of distant metastases (hazard ratio HR = 1.7; 95% CI 0.9–3.3) as compared to patients with normal bodyweight (18.5 ≤ BMI < 25 kg/m2, n = 209), overweight (25 ≤ BMI <30 kg/m2, n = 257) or obesity class I (30 ≤ BMI <35 kg/m2, n = 102). There were no significant differences for local recurrence. Conclusions: Underweight and excess bodyweight are associated with lower overall survival and higher rates of distant metastasis in patients with rectal cancer.

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