scholarly journals Lack of Pathological Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy is Associated with Poorer Long-Term Oncological Outcomes

2019 ◽  
pp. 1-6
Author(s):  
Shmuel Avital ◽  
Debora Kidron ◽  
Lauren Lahav ◽  
Liron Berkovich ◽  
Moshe Mishaeli ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Pathological Response ◽  
Preoperative Treatment

Purpose: Tumor regression scores are used to evaluate local response to preoperative treatment. Complete pathological response (tumor regression score=0) is associated with excellent prognosis. In this study we evaluated the prevalence and impact of poor-to-no pathological response to neoadjuvant treatment (tumor regression score=3), based on a recently revised grading system on long term oncologic outcomes among rectal cancer patients. Methods: This retrospective study included rectal cancer patients who received. neoadjuvant chemoradiotherapy and surgical resection at our medical center. Pathological specimens were ren evaluated and graded (grades 0-3) based on the revised tumor regression scores. Disease free survival and cancer specific survival rates were documented and matched with the patients’ tumor regression scores. Results: Initially 78 patients were included. 6 patients were later excluded from the long-term follow up since they developed disease progression during neoadjuvant treatment. Among the other 72 patients, 38 (52.8%) were classified as tumor regression score=3 (no response) and 34 (47.2%) tumor regression score=0-2 (any level of response). Conversion from laparoscopy to open surgery was higher in the tumor regression score=3 group (21% vs. 2.9%, p=0.02). Follow-up ranged from 5 months to 12 years. Nine (12.5%) patients experienced disease recurrence, 8 with tumor regression score=3. Most recurrences were metastases to liver and lungs. Disease free survival was lower in tumor regression score=3 patients as compared to tumor regression score=0-2. Conclusions: Non-responders to neoadjuvant therapy are at higher risk for disease recurrence, conversion to open surgery and disease-related mortality. Systemic recurrence of tumor regression score=3 tumors suggests an aggressive biology of these tumors. Further studies are needed to characterize tumors that are less likely to respond to radiotherapy and to personalize preoperative treatment decisions.

Oncologic Outcomes of ypT1-3N0 mid-Low Rectal Cancer Compared with pT1-3N0 Disease After Radical Resection

2020 ◽  
Author(s):  
Hong Yang ◽  
Jiabo Di ◽  
Ming Cui ◽  
Jiadi Xing ◽  
Chenghai Zhang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Radical Resection ◽  
Low Rectal Cancer ◽  
Oncologic Outcomes ◽  
Cancer Specific Survival ◽  
The Difference

Abstract Background: Neoadjuvant chemoradiotherapy (CRT) can downstage rectal carcinoma, resulting in superior resectability, better local control and survival benefits. However, it is unclear whether patients treated with CRT and those who did not have similar outcomes at the same pathological stage. This study aimed to investigate the long-term outcomes of ypT1-3N0 mid-low rectal cancer who received neoadjuvant CRT followed by total mesorectal excision (TME) compared with pT1-3N0 rectal cancer immediately managed with surgery. Methods: We retrospectively enrolled 180 patients with pT1-3N0 or ypT1-3N0 rectal cancer located within 10cm from the anal edge who underwent TME between 2009 and 2015. Of these patients, 63 received neoadjuvant CRT, while 117 underwent radical proctectomy without preoperative therapy. The disease-free survival (DFS) and cancer-specific survival (CSS) were compared between the two groups. Results: Within a median follow-up time of 65 months, the 5-year DFS was lower in the CRT group than the non-CRT group (74.9% vs. 92.6%, P=0.001), and the 5-year CSS presented a similar trend as well (89.6 % vs. 97.1%, P=0.054). By subgroup analysis, the difference in DFS and CSS was mainly caused by the difference between ypT3N0 and pT3N0 disease (71.1% vs. 96.1%, P＜0.001 and 90.9% vs. 100%, P=0.029, respectively). However, patients with ypT1-2N0 had an analogous prognosis to those with pT1-2N0 disease (77.9% vs. 89.0%, P=0.225 and 88.1% vs. 94.2%, P=0.292, respectively). Multivariate analysis indicated that neoadjuvant CRT was not an independent predictor of DFS. Conclusion: After neoadjuvant CRT followed by TME, patients with ypT1-2N0 rectal cancer had an analogous prognosis to those with initial pT1-2N0 disease, whereas patients with ypT3N0 rectal cancer had worse prognosis compared with that of pT3N0 disease.

scholarly journals Prognostic Value of Mandard and Dworak Tumor Regression Grading in Rectal Cancer: Study of a Single Tertiary Center

ISRN Surgery ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Marisa D. Santos ◽  
Cristina Silva ◽  
Anabela Rocha ◽  
Eduarda Matos ◽  
Carlos Nogueira ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Prognostic Value ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Disease Recurrence ◽  
Regression Grading ◽  
Survival Difference ◽  
Tertiary Center

Goal. To evaluate the prognostic value of Mandard and Dworak grading systems regarding neoadjuvant chemoradiotherapy (CRT) response on rectal cancer. Materials and Methods. We queried our center’s database for patients with colo rectal cancer with locally advanced rectal cancer (LARC) who received neoadjuvant CRT followed by total mesorectum excision (TME) between 2003 and 2011. After excluding 18 patients from the initial query the remaining 139 were reassessed for disease recurrence and survival; the specimens’ slides were reviewed and classified according to two tumor regression grading (TRG) systems: Mandard and Dworak. Based on these TRG scores, two patient groups were created: patients with good response versus patients with bad response (Mandard TRG1+2 versus Mandard TRG3+4+5 and Dworak TRG4+3 versus Dworak TRG2+1+0). Overall survival (OS), disease-free survival (DFS), and disease recurrence were then evaluated. Results. Mean age was 64.2 years and median follow up was 56 months. No significant survival difference was found when comparing patients with Dworak TRG 4+3 versus Dworak TRG2+1+0 (P=0.10). Mandard TRG1+2 presented with significantly better OS and DFS than Mandard TRG3+4+5 (OS P=0.013; DFS P=0.007). Conclusions. Mandard system provides higher accuracy over Dworak system in predicting rectal cancer prognosis when neoadjuvant CRT is applied for tumor regression.

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

Rectal cancer – current treatment strategy and the tumor regression grade evaluation after neoadjuvant therapy in patients who underwent surgery at the I. Department of Surgery, General University Hospital in Prague between 2012 and 2016

2021 ◽  
Vol 100 (2) ◽  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Tumor Regression ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Current Treatment ◽  
University Hospital ◽  
Tumor Regression Grade ◽  
Oncological Treatment ◽  
Regression Grade

Introduction: The article contains a summary of the issues of staging and therapy with an emphasis on the neoadjuvant treatment and associated tumor regression grade with the analysis of our own group of patients. Methods: Retrospective analysis of patients with rectal cancer who underwent a surgery at the 1st Department of Surgery – Thoratic, Abdominal and Injury Surgery; First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic, focusing on those who underwent neoadjuvant chemoradiotherapy and their pathologists evaluated tumor regression grade after the resection. Results: The group consists of 161 patients operated on between 2012 and 2016. 47 patients underwent neoadjuvant oncological treatment with further evaluation of the tumor regression grade by a pathologist, a scoring system according to Ryan was used. A complete pathological response was elicited in 10.4% of patients, no response in 35.4% of patients, and partial tumor regression in 54.2%. Conclusion: Although there is a difference in our results compared to foreign publications, the proportion of patients remains comparable. Studies evaluating the advantages versus disadvantages of neoadjuvant therapy will certainly follow, and the question of the suitability of surgical treatment as the only curative solution is partially raised.

scholarly journals Local environment in biopsy better predict the pathological response to neoadjuvant chemoradiotherapy in rectal cancer

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Yan Huang ◽  
Xiao-ying Lou ◽  
Ya-xi Zhu ◽  
Yu-chen Wang ◽  
Lei Zhang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Response ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Pathological Response ◽  
Local Tumor ◽  
Independent Predictive Factor ◽  
Tumor Environment ◽  
The Impact

Abstract Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Here, we analyzed the impact of local and systemic environments on the tumor response to preoperative chemoradiotherapy in rectal cancer. We recruited 141 patients with rectal cancer treated with nCRT. We evaluated the local tumor environment, including tumor-infiltrating lymphocytes (TILs), intratumor budding (ITB), and the systemic inflammatory environment, including the neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) level. Our finding revealed that tumor regression was significantly associated with the density of CD8+ TILs in the intraepithelial, the presence of ITB, the combination of NLR and CRP (NLR-CRP) value, and the combination of CD8+ intraepithelial TIL (iTIL) density and ITB presence. Moreover, multivariate analysis showed that only the combination of CD8+ iTILs and ITB was an independent predictive factor for the pathological response to nCRT in rectal cancer. Our finding demonstrate that the local tumor environment was a better predictor of the tumor response than the systemic environment and thus provided new insight into screening for patients who are more likely to benefit from cancer treatment.

Impact of biomarker dynamic profile and pathological response induced by neoadjuvant chemoradiotherapy in rectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3614-3614
Author(s):  
A. L. Gentile ◽  
C. Pinto ◽  
C. Ceccarelli ◽  
F. Di Fabio ◽  
C. Funaioli ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Neoadjuvant Treatment ◽  
Rectal Adenocarcinoma ◽  
Neoadjuvant Chemoradiotherapy ◽  
Rectal Surgery ◽  
Pathological Response ◽  
Resection Margins ◽  
Tumor Regression Grade ◽  
Operative Specimen

3614 Background: The aim of this study was to evaluate the correlation among biomarkers, pathological response and clinical outcomes in patients (pts) with rectal cancer submitted to neoadjuvant chemoradiotherapy. Methods: Pts entering the study had rectal adenocarcinoma, uT3/4N-/+ or uT2N-/+ with inferior location. Chemotherapy consisted of oxaliplatin 60 mg/m2 weekly infusion IV for 6 times and 5-fluorouracil 225 mg/m2/die continuous infusion IV d 1–38. Radiotherapy was delivered up to a dose of 50.4 Gy in daily fractions of 1.8 Gy d 1–38. Rectal surgery with TME was performed 6–8 weeks after neoadjuvant treatment. Immunohistochemical determination of Ki67, p53, bcl2, TS, EGFR, MLH1 and MSH2 was performed in pretreatment biopsy and operative specimen. Results: Between March 2002 and May 2005, 32 pts had completed neoadjuvant therapy and surgery. Pt characteristics: 24 (75%) men and 8 (25%) women; median age 64 (33–80) years; stage uT2N-M0 3 (9.4%) pts, uT3N-M0 14 (43.8%), uT3N+M0 10 (31.2%), uT3NXM0 2 (6.2%), uT4N+M0 3 (9.4%). Surgery consisted of abdominal-perineal amputation in 12 (37.5%) and low-anterior resection in 17 (53.1%) pts, with negative circumferential resection margins in 86.2%. Laparoscopic local excision was performed in 3 (9.4%) pts. Pathological down-staging occurred in 18 (56.2%) pts, including 7 (21.9%) pT0N0, with sphincter preservation in 40%. Tumor Regression Grade (TRG) (according to Mandard) evaluation of operative specimen was: 7 TRG1, 11 TRG2, 11 TRG3 and 3 TRG4. Expression mean value in pretreatment biopsy and operative specimen was: Ki67 88.8% and 31.7%; p53 49.7% and 40.7%; TS 12.6% and 10.0%; MLH1 89.7% and 76.4%; MSH2 84.3% and 72.2%. The evaluation of biomarker profile in operative specimen of TRG2 pts vs TRG3–4 showed: Ki67 16.6% vs 46.2% (p=0.03); TS 4.5% vs 12.9% (ns); MSH2 82.3% vs 65.6% (ns); p53 52.3% vs 34.8% (ns). Median DFS was 19 (3–35) months. At a median follow-up of 22 (5–41) months, 100.0% of TRG1 pts, 90.9% of TRG2, 73.3% of TRG3–4 had no-evidence of disease relapse. Conclusions: These preliminary results suggest a correlation between Ki67 and pathological response in rectal cancer pts treated with neoadjuvant therapy. Moreover, DFS appears to be related to TRG. No significant financial relationships to disclose.

Polymorphisms of thymidylate synthase as prognostic factor in rectal cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 433-433
Author(s):  
V. Arrazubi ◽  
J. Suarez ◽  
D. Guerrero ◽  
K. Cambra ◽  
M. L. Gomez Dorronsoro ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Thymidylate Synthase ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumour Regression ◽  
The Difference

433 Background: Neoadjuvant fluoropyrimidine-based chemotherapy (ChT) plus radiotherapy (Rt) is a standard approach for locally advanced rectal cancer. Polymorphisms of thymidylate synthase (TS), the target for fluoropyrimidines, are recognized prognostic factors in colon cancer. The aim of this study was to evaluate the prognostic value of the polymorphisms of TS in rectal cancer after neoadjuvant ChT plus Rt. Methods: We studied one-hundred consecutive patients with stage II/III rectal cancer between November 2001 and March 2009. Patients underwent surgery 6-8 weeks after neoadjuvant Rt (5,040 cGy) plus fluoropyrimidine-based ChT. DNA was extracted from paraffin embedded biopsies. TS1494del6 and 5′-28bp repeat +G/C SNP polymorphisms were determined. Results: Sixty-seven percent were men and median age was 67 years. ypT stage was: T0 9%, T1 2%, T2 27%, T3 60% and T4 2%; 32% had locoregional adenopathies. The median follow-up was 45 months and relapse occurred in 20% of patients. Polimorphisms could be determined in 98% of pt: -6bp/-6bp 10%, - 6bp/+6bp 39%, +6bp/+6bp 51% and 2R/2R 72%, 2R/3R 21%, 3R/3R 6%. The grade of pathological tumour regression was not associated with polymorphisms. Relapses occurred in 40% of patients -6bp/-6bp, 22% of patients -6bp/+6bp and 21% of patients +6bp/+6bp. The difference in disease- free survival (DFS) between the first and the third groups was stadistically significative (p=0.049). No relation between 5′-28bp repeat +G/C SNP polymorphism and DFS was found. Conclusions: Our data suggest that the TS1494del6 polimorphism may be an important prognosis factor in rectal cancer receiving neoadjuvant chemoradiotherapy. No significant financial relationships to disclose.

Neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Predicting long-term outcomes based on response to treatment.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 621-621
Author(s):  
Kirsten Elizabeth Jean Laws ◽  
Christina Wilson ◽  
David McIntosh ◽  
Stephen Harrow
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Preoperative Staging ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Combined Modality Treatment ◽  
Long Term Outcomes ◽  
Node Positive ◽  
Long Course

621 Background: Neoadjuvant long course chemoradiotherapy is well recognised as a standard treatment in locally advanced, margin threatening rectal cancer, in order to downstage and reduce local recurrence. We investigated retrospectively whether long term outcomes could be predicted by response to neoadjuvant treatment, and which factors specifically seemed to predict a risk of poorer outcome. Methods: All patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified retrospectively. Patients were excluded if the treatment indication was for inoperable disease, postoperative, recurrence, or palliative intent. A total of 231 patients were analysed with retrospective analysis of all electronic records and case notes. The following information was collated: preoperative staging, chemoradiotherapy treatment planned and received, operation performed, postoperative pathology (including nodal status, margins, presence of LVSI, and evidence of response to neoadjuvant treatment), disease free survival, and overall survival. Results: Kaplan Meier curves are presented showing patients with either a complete or partial response to neoadjuvant treatment appear to have a statistically significant improvement in long term outcomes, compared to those with no response (Mean survival 55 months, 56 months and 43months respectively, p<0.01). Furthermore, those who remain node positive or have evidence of LVSI following neoadjuvant treatment appear to have a statistically significant poorer outcome. Conclusions: Our study further develops on previous work looking at the prediction of outcomes following response to neoadjuvant treatment in rectal cancer. It appears that those who respond to initial treatment will have a better outcome than those who do not, including those who remain node positive or with LVSI following treatment. This study is limited because it is retrospective. Randomised controlled trial data is required to enable identification of poor risk imaging and pathology features that might suggest the need for adjuvant therapy following combined modality treatment with neoadjuvant chemoradiotherapy and surgery.

The prognosis valve of tumor regression grade in the same ypStage patients after neoadjuvant treatment in locally advanced rectal cancer: Post-hoc analysis of a prospective trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16129-e16129
Author(s):  
Jianwei Zhang ◽  
Yue Cai ◽  
Huabin Hu ◽  
Zehua Wu ◽  
Xiaoyu Xie ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Prospective Trial ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
Prognosis Factor

e16129 Background: The ypStage after neoadjuvant treatment was an important prognosis factor in locally advanced rectal cancer (LARC). pCR or ypStage 0 showed best prognosis, while ypStage II-III showed poor prognosis and further adjuvant chemotherapy with FOLFOX was recommended. Tumor regression grade (TRG) was another factor to evaluate the response to neoadjuvant treatment. Even in the same ypStage, the TRG could be different. Here, we tried to analyze the prognosis valve of TRG in the same ypStage after neoadjuvant treatment in LARC from a prospective trial (FOWARC study). Methods: Patients with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil plus radiotherapy followed by surgery and seven cycles of infusional fluorouracil as adjuvant treatment, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). Survival analysis was performed on different ypStage and TRG (WHO classification) group. Results: In total, 495 patients were randomly assigned to different neoadjuvant treatment. 444 patients received surgery with a median follow-up of 45.2 months. The 3-year disease free survival (DFS) in ypStage 0, ypStage I, ypStage II and ypStage III was 95.8%, 89.2%, 71.7% and 55.1%, respectively (P < 0.0001). In TRG 0, 1, 2 and 3, the 3-year DFS was 93.3%, 83.2%, 68.4% and 63.6%, respectively (P < 0.0001). In ypStage I subgroup, TRG was not an independent prognosis factor, the 3-year DFS for TRG 1, 2 and 3 was 90.0%, 90.7% and 76.2%, respectively (P = 0.277). In ypStage II population, the 3-year DFS for TRG 1, 2 and 3 was 78.6%, 70.3% and 64.7%, respectively (P = 0.184). The ypStage III group showed great heterogeneity, the 3-year DFS for TRG 0-3 was 60.0%, 70.0%, 41.8% and 59.5%, respectively (P = 0.067). Conclusions: Both ypStage and TRG was strong prognosis factor for rectal cancer after neoadjuvant treatment. However, TRG was not an independent prognosis factor in the same ypStage after neoadjuvant treatment. Clinical trial information: NCT01211210 .

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