scholarly journals Prognostic Impact of An Integrative Landscape of Clinical, Immune, and Molecular Features in Non-Metastatic Rectal Cancer

2022 ◽  
Vol 11 ◽  
Author(s):  
Soledad Iseas ◽  
Juan M. Sendoya ◽  
Juan Robbio ◽  
Mariana Coraglio ◽  
Mirta Kujaruk ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Disease Free Survival ◽  
Poor Responders ◽  
Prognostic Impact ◽  
Free Survival ◽  
Molecular Features ◽  
Mutational Status ◽  
Cluster 2

Rectal Cancer (RC) is a complex disease that involves highly variable treatment responses. Currently, there is a lack of reliable markers beyond TNM to deliver a personalized treatment in a cancer setting where the goal is a curative treatment. Here, we performed an integrated characterization of the predictive and prognostic role of clinical features, mismatch-repair deficiency markers, HER2, CDX2, PD-L1 expression, and CD3−CD8+ tumor-infiltrating lymphocytes (TILs) coupled with targeted DNA sequencing of 76 non-metastatic RC patients assigned to total mesorectal excision upfront (TME; n = 15) or neoadjuvant chemo-radiotherapy treatment (nCRT; n = 61) followed by TME. Eighty-two percent of RC cases displayed mutations affecting cancer driver genes such as TP53, APC, KRAS, ATM, and PIK3CA. Good response to nCRT treatment was observed in approximately 40% of the RC cases, and poor pathological tumor regression was significantly associated with worse disease-free survival (DFS, HR = 3.45; 95%CI = 1.14–10.4; p = 0.028). High neutrophils-platelets score (NPS) (OR = 10.52; 95%CI=1.34–82.6; p = 0.025) and KRAS mutated cases (OR = 5.49; 95%CI = 1.06–28.4; p = 0.042) were identified as independent predictive factors of poor response to nCRT treatment in a multivariate analysis. Furthermore, a Cox proportional-hazard model showed that the KRAS mutational status was an independent prognostic factor associated with higher risk of local recurrence (HR = 9.68; 95%CI = 1.01–93.2; p <0.05) and shorter DFS (HR = 2.55; 95%CI = 1.05–6.21; p <0.05), while high CEA serum levels were associated with poor DFS (HR = 2.63; 95%CI = 1.01–6.85; p <0.05). Integrated clinical and molecular-based unsupervised analysis allowed us to identify two RC prognostic groups (cluster 1 and cluster 2) associated with disease-specific OS (HR = 20.64; 95%CI = 2.63–162.2; p <0.0001), metastasis-free survival (HR = 3.67; 95%CI = 1.22–11; p = 0.012), local recurrence-free survival (HR = 3.34; 95%CI = 0.96–11.6; p = 0.043) and worse DFS (HR = 2.68; 95%CI = 1.18–6.06; p = 0.012). The worst prognosis cluster 2 was enriched by stage III high-risk clinical tumors, poor responders to nCRT, with low TILs density and high frequency of KRAS and TP53 mutated cases compared with the best prognosis cluster 1 (p <0.05). Overall, this study provides a comprehensive and integrated characterization of non-metastatic RC cases as a new insight to deliver a personalized therapeutic approach.

Evaluation of response after chemoradiation for rectal cancer as a predictive factor for the benefit of adjuvant chemotherapy: A pooled analysis of 2,724 individual patients.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 361-361 ◽  
Author(s):  
G. L. Beets ◽  
M. Maas ◽  
P. J. Nelemans ◽  
V. Valentini ◽  
C. H. Crane ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Individual Patient Data ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Patient Data ◽  
Cox Proportional Hazards Model ◽  
Poor Responders ◽  
Free Survival ◽  
Disease Free

361 Background: Neoadjuvant chemoradiation (CRT) for rectal cancer increasingly results in pathologic response. It has been suggested that patients with different degrees of response might not have the same benefit of adjuvant chemotherapy. The aim was to determine whether patients with a pathologic complete response (pCR), ypT1-2 or ypT3-4 tumor after CRT for rectal cancer have different benefits of adjuvant chemotherapy for disease-free survival. Methods: Authors from studies evaluating different degrees of response to CRT were contacted to share individual patient data. The collected individual patient data were pooled into one dataset. To evaluate the effect of adjuvant chemotherapy on disease-free survival multivariate analyses according to the Cox proportional hazards model were performed. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for 3 subgroups: patients with pCR(ypT0N0), ypT1-2 tumor and ypT3-4 tumor after CRT. To determine benefit of adjuvant chemo for different pathologic N-stages we performed subgroup analyses. Results: 2,724 patients were included. 811 had pCR (28%), 863 had ypT1-2 (30%) and 1050 had ypT3-4 (37%). Median follow-up was 50 months (range 0-277). 41% underwent adjuvant chemotherapy, which consisted mostly of 5-FU based chemotherapy. The HR with 95%CI for disease-free survival for adjuvant chemotherapy was 0.94 (0.50-1.78) for patients with pCR, 0.61 (0.40-0.92) for patients with ypT1-2 tumors and 0.97 (0.75-1.25) for patients with ypT3-4 tumors. ypT1-2N0 patients benefited most from adjuvant chemo: HR 0.45 (0.27-0.75) vs. 0.79 (0.31-1.95) for patients with ypT1-2N+. For ypT3-4 patients pN-stage did not alter benefit of adjuvant chemo. Conclusions: Patients with pCR or ypT3-4 residual tumor after CRT do not seem to benefit from adjuvant chemo. This might be due to the already good prognosis of patients with pCR and less responsiveness to 5-FU based chemotherapy in the poor responders (the ypT3-4 tumors). Possibly adjuvant chemotherapy can be omitted or adapted for these patients. Patients with ypT1-2N0 benefit most from adjuvant chemo. No significant financial relationships to disclose.

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.

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.

scholarly journals Adjuvant chemotherapy for poor-responders to neoadjuvant therapy in locally advanced rectal cancer: does it improve the prognosis?

2021 ◽  
Author(s):  
KHADIJA DARIF ◽  
ZINEB BENBRAHIM ◽  
JIHANE CHOUEF ◽  
ZAYNAB MAHDI ◽  
ADIL NAJDI ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Poor Responders ◽  
Free Survival ◽  
Radio Chemotherapy

Abstract Background: Colorectal cancer is the first cause of cancer death in developed countries. Although colon and rectal cancers are frequently grouped as a single disease entity, these malignancies have important differences in treatment approaches ; The preoperative radio-chemotherapy combination has become the standard for tumors of the middle and lower rectum, improving local control. But unlike colon cancer, currently there is no compelling evidence of the benefit of adjuvant chemotherapy in rectal cancer. This study examines the role of adjuvant chemotherapy after a neoadjuvant treatment and chirurgy in localy advanced rectal cancer, especially in poor responders to neoadjuvant therapy. Patients and Methods: Using the medical files collected at the medical oncology department at the Hassan II Hospital Center in Fez , Morocco; patients with rectal cancer diagnosed in 2014 through 2019 who received neoadjuvant CRT(concomitant radio chemotherapy) and surgery with or without AC(adjuvant chemotherapy) were identified. Kaplan-Meier analysis, log-rank tests were used to assess survival. Results: A total of 90 patients were identified; 70 received AC and 20 did not (observation [OBS] group). Median overall survival(OS) of the general population was 40 months, CI 95% = [25-56], the median disease-free survival (DFS) was 17 months,CI 95% = [7-26]. In the analysis of survival according to the ypT and ypN subgroups: the median OS in the ypT1-2 and ypN0 subgroup was higher than in the ypT3-4 or ypN + group (40 months vs 33 months and 44 months vs. 31 consecutive months); DFS was also better in the ypT1-2 and ypN0 group (29 months vs. 11 months (p = 0.05) and 29 months vs. 13 months respectively).The median OS was 40 months for AC and 23 months for OBS (p = 0.036), by against there was no significant improvement in recurrence-free survival. Conclusions: In this population of patients with LARC (localy advanced rectal cancer) treated with neoadjuvant CRT and surgery,

Local recurrence after rectal cancer resection is strongly related to the plane of surgical dissection and is further reduced by pre-operative short course radiotherapy. Preliminary results of the Medical Research Council (MRC) CR07 trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 3512-3512 ◽  
Author(s):  
P. Quirke ◽  
D. Sebag-Montefiore ◽  
R. Steele ◽  
S. Khanna ◽  
J. Monson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Disease Free Survival ◽  
Rank Test ◽  
Surgical Specimen ◽  
Free Survival ◽  
Short Course ◽  
Quality Of Surgery ◽  
Disease Free

3512 Background: The MRC CR07 trial compared routine short course pre-operative radiotherapy (PRE) with selective post-operative chemo-radiation if there was involvement of the circumferential resection margin (CRM) (POST) and included a prospective pathological assessment of the quality of resection of the surgical specimen. Methods: A total of 1350 patients were randomised from 52 centres between March 1998 and August 2005. Median follow-up is 3 years. Trial pathologists were trained in histopathological assessment and reporting of the involvement of the CRM and plane of surgery (PoS) according to pre-set criteria describing the plane of dissection (Grade 1-muscularis plane: 2-intramesorectal plane: 3-mesorectal plane). 1232 patients were prospectively assessed for CRM and 1119 for PoS. Results: The CRM was involved (tumour ≤1mm) in 139 (11%) of resected specimens, and for these patients the 3-year local recurrence (LR), disease-free survival (DFS) and overall survival rates were 18%, 50% and 57%. For the 1093 patients with CRM-ve the respective rates were 7%, 81% and 84%. LR and DFS rates were associated with PoS (log-rank test p=0.0019 and p=0.0506 respectively), and in addition there was clear evidence of a reduction in LR and improvement in DFS rates in favour of PRE for all grades of quality of surgical assessment as shown in the table . Conclusions: The results indicate a strong association between the quality of surgery and the rates of local recurrence and disease-free survival, as well as a clear benefit from the addition of PRE to all grades of surgical dissection. Thus for patients with rectal cancer short-course pre-operative radiotherapy and good quality surgery can almost completely eliminate local recurrence. [Table: see text] No significant financial relationships to disclose.

scholarly journals Local Recurrence in Patients with Upper Third Rectum Cancer Treated with Surgery Alone Compared with Surgery Plus Chemoradiotherapy

2020 ◽  
pp. 1-6
Author(s):  
Uriel Martinez ◽  
Beatriz Mota ◽  
David Rayas ◽  
Jesús Sansón ◽  
Manuel Martínez ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Multimodal Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Rectum Cancer ◽  
Historical Cohort ◽  
Free Survival ◽  
Upper Third ◽  
Disease Free

Background: Colorectal cancer is the third most common neoplasm in Mexico, rectal cancer is the 16th most common neoplasm [1]. Due to the different behavior and prognostic factors of locally advance disease, manage should be tailored by a multidisciplinary approach. In tumors that rise in the upper third rectum cancer scenario there are no studies comparing the oncological results of multimodal treatment vs surgery alone. Objective: To compare the disease-free survival in patients with upper third rectal cancer treated with surgery alone vs multimodal treatment. Material and Methods: We conducted a descriptive, retrospective, longitudinal study using an historical cohort. Analysis was based from the information in patient`s records from diagnosed with cancer of the upper third rectum from 2011 to 2016. All patients with diagnosis of upper third rectum cancer were set in to two groups according to the treatment modality recited: Surgery alone and neoadjuvant chemotherapy. The records of patients diagnosed with cancer of the upper third rectum were reviewed and divided into two groups: with and without neoadjuvant chemoradiotherapy, both treated with surgery. Results: A total of 64 patient`s record were eligible, 48 of them were treated with surgery alone and 16 with a multimodal approach. The mean age was 65.5 years in those treated with surgery and 69 in the multimodal management group. The most frequent procedure was anterior resection, 45 cases (70.3%) in the group treated with surgery and 12 cases (18.7%) in the multimodal group. A case of complete pathological response was reported after a follow up of two years. Conclusion: The data suggests that there are no statistically significant differences in the local recurrence and disease-free survival with the use of neoadjuvant chemoradiotherapy.

Disease-free Survival and Local Recurrence After Laparoscopic-assisted Resection or Open Resection for Rectal Cancer

2019 ◽  
Vol 269 (4) ◽  
pp. 596-602 ◽  
Author(s):  
Andrew R. L. Stevenson ◽  
Michael J. Solomon ◽  
Christopher S. B. Brown ◽  
John W. Lumley ◽  
Peter Hewett ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Disease Free Survival ◽  
Open Resection ◽  
Free Survival ◽  
Laparoscopic Assisted ◽  
Disease Free

Intersphincteric Resection for Low Rectal Cancer: Parameters Affecting Functional Outcomes and Survival Rates

2021 ◽  
Vol 39 ◽  
Author(s):  
Vusal Aliyev ◽  
◽  
Beslen Goksoy ◽  
Suha Goksel ◽  
Koray Guven ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Functional Outcomes ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Intersphincteric Resection ◽  
Low Rectal Cancer ◽  
Free Survival ◽  
Very Low Rectal Cancer ◽  
Disease Free

Introduction: The development of new surgical techniques and devices, as well as the improvements in neoadjuvant chemoradiotherapy enabled intersphincteric resection (ISR), has reduced permanent colostomy usage. The aim of this study was to assess the long-term oncological and functional outcomes of patients who underwent partial ISR for rectal cancer located less than 5cm from the anal verge. Materials and Methods: A series of 106 consecutive patients with very low rectal cancer underwent curative partial ISR from January 2006 to September 2019 were retrospectively evaluated. One-hundred-three (97%) of 106 patients received neoadjuvant chemo-radiotherapy. Overall survival (OS), disease-free survival (DFS), and local recurrence (LR) rates were calculated using Kaplan–Meier methods. The Wexner incontinence score and Kirwan classification were used to evaluate patients’ functional results. Results: The median follow up was 60 months (range, 18–174). The estimated five-year overall and disease-free survival rates were 89% and 81.6%, respectively. Five-year local recurrence and distant metastasis rates were 6.6% and 10.4%, respectively. There was no in-hospital and 30-day mortality. The median Wexner score was 9 (range, 0–20) for 72 patients. Age (<65 years, p=0.027) and gender (male, p=0.019) had a positive effect on functional outcomes after surgery. One and five years colostomy-free survival rates were 96% and 89%, respectively. Conclusion: Intersphincteric resection techniques are feasible for patients with very low rectal cancer, providing good oncological and functional outcomes.

Effect of extent of anterior resection and sex on disease-free survival and local recurrence in patients with rectal cancer

1994 ◽  
Vol 81 (8) ◽  
pp. 1227-1229 ◽  
Author(s):  
L. M. D. Buhre ◽  
N. H. Mulder ◽  
A. J. de Ruiter ◽  
A. J. van Loon ◽  
R. C. J. Verschueren
Keyword(s):  
Rectal Cancer ◽  
Local Recurrence ◽  
Anterior Resection ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free
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