The role of local excision in rectal cancer after complete response to neoadjuvant treatment

2007 ◽  
Vol 16 ◽  
pp. 101-104 ◽  
Author(s):  
C. Coco ◽  
A. Manno ◽  
C. Mattana ◽  
A. Verbo ◽  
G. Rizzo ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Excision ◽  
Neoadjuvant Treatment ◽  
Complete Response

scholarly journals CEA, EpCAM, αvβ6 and uPAR Expression in Rectal Cancer Patients with a Pathological Complete Response after Neoadjuvant Therapy

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 516
Author(s):  
Daan Linders ◽  
Marion Deken ◽  
Maxime van der Valk ◽  
Willemieke Tummers ◽  
Shadhvi Bhairosingh ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Cancer Patients ◽  
Pathological Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Response Evaluation ◽  
Tumor Bed ◽  
Upar Expression ◽  
Diagnostic Biopsy

Rectal cancer patients with a complete response after neoadjuvant therapy can be monitored with a watch-and-wait strategy. However, regrowth rates indicate that identification of patients with a pathological complete response (pCR) remains challenging. Targeted near-infrared fluorescence endoscopy is a potential tool to improve response evaluation. Promising tumor targets include carcinoembryonic antigen (CEA), epithelial cell adhesion molecule (EpCAM), integrin αvβ6, and urokinase-type plasminogen activator receptor (uPAR). To investigate the applicability of these targets, we analyzed protein expression by immunohistochemistry and quantified these by a total immunostaining score (TIS) in tissue of rectal cancer patients with a pCR. CEA, EpCAM, αvβ6, and uPAR expression in the diagnostic biopsy was high (TIS > 6) in, respectively, 100%, 100%, 33%, and 46% of cases. CEA and EpCAM expressions were significantly higher in the diagnostic biopsy compared with the corresponding tumor bed (p < 0.01). CEA, EpCAM, αvβ6, and uPAR expressions were low (TIS < 6) in the tumor bed in, respectively, 93%, 95%, 85%, and 62.5% of cases. Immunohistochemical evaluation shows that CEA and EpCAM could be suitable targets for response evaluation after neoadjuvant treatment, since expression of these targets in the primary tumor bed is low compared with the diagnostic biopsy and adjacent pre-existent rectal mucosa in more than 90% of patients with a pCR.

PO-1089: Major and complete response after neoadjuvant treatment in rectal cancer: a retrospective analysis

2020 ◽  
Vol 152 ◽  
pp. S576-S577
Author(s):  
M. Giraffa ◽  
G. Chiloiro ◽  
E. Meldolesi ◽  
B. Corvari ◽  
C. Coco ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Retrospective Analysis ◽  
Neoadjuvant Treatment ◽  
Complete Response

A multicenter phase Ib/II study of DNA-PK inhibitor peposertib (M3814) in combination with capecitabine and radiotherapy in patients with locally advanced rectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS144-TPS144
Author(s):  
Paul Bernard Romesser ◽  
Emma B. Holliday ◽  
Tony Philip ◽  
Rocio Garcia-Carbonero ◽  
Jaume Capdevila ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib

TPS144 Background: Perioperative radiotherapy and chemotherapy, followed by total mesorectal excision, is the standard of care for patients with locally advanced rectal cancer (LARC). However, 1/3 of these patients still develop distant metastases, indicating the need for more effective therapies. In addition, strategies that increase pathological complete response rates are needed to enable non-surgical management of LARC. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway for double-strand break repair. Peposertib (M3814), a potent, selective, orally administered DNA-PK inhibitor, has been shown to potentiate the effect of ionizing radiation in a human colon cancer xenograft model and several colon cancer cell lines. Peposertib is being investigated in several different trials across multiple indications. This Phase Ib/II study (NCT03770689) aims to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of the neoadjuvant treatment combination of peposertib, capecitabine, and radiotherapy (RT) in patients with LARC. Methods: Patients aged ≥18 years with histologically confirmed and resectable Stage II/III rectal adenocarcinoma are eligible. Induction chemotherapy is permitted, but residual disease must first be documented by MRI, digital rectal examination and endoscopy. Patients who received other anticancer therapies or those with prior pelvic RT are excluded. At open-label Phase Ib (open), 18–30 patients (n = 3 per cohort) will receive peposertib + capecitabine (orally, 825 mg/m2 twice daily [BID]) + RT (45–50.4 Gy), 5 days/week. Peposertib 50 mg once daily (QD) was the starting dose. Additional dose levels will range between 100─800 mg QD. Dose escalation is determined by the safety monitoring committee and guided by a Bayesian 2-parameter logistic regression model. At Phase II (planned), 150 patients will be randomized (1:1) to receive oral capecitabine (825 mg/m2 BID) + RT (45–50 Gy), with either oral peposertib (recommended phase II dose [RP2D] or placebo, QD for 5 days/week. Primary objectives are to define a maximum tolerated dose and RP2D (Phase Ib), and to evaluate the efficacy of peposertib + capecitabine + RT in terms of pathological/clinical complete response (Phase II). Secondary objectives include assessment of antitumor activity (Phase Ib), quality of life outcomes (Phase II), and PK of peposertib, and the safety and tolerability of the combination therapy (both phases). To date, one patient has received peposertib 50 mg QD, six patients peposertib 100 mg QD, three patients peposertib 150 mg QD, and three patients peposertib 250 mg QD. Clinical trial information: NCT03770689.

scholarly journals Pathological Complete Response Following Different Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer: A Systematic Review and Meta-analysis

2020 ◽  
Vol 27 (11) ◽  
pp. 4319-4336 ◽  
Author(s):  
S. Hoendervangers ◽  
J. P. M. Burbach ◽  
M. M. Lacle ◽  
M. Koopman ◽  
W. M. U. van Grevenstein ◽  
...  
Keyword(s):  
Systematic Review ◽  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Treatment Strategies ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Abstract Background Pathological complete response (pCR) following neoadjuvant treatment for locally advanced rectal cancer (LARC) is associated with better survival, less local recurrence, and less distant failure. Furthermore, pCR indicates that the rectum may have been preserved. This meta-analysis gives an overview of available neoadjuvant treatment strategies for LARC and analyzes how these perform in achieving pCR as compared with the standard of care. Methods Pubmed, Embase, and Cochrane Central bibliographic databases were searched. Randomized controlled trials in which patients received neoadjuvant treatment for MRI-staged nonmetastatic resectable LARC were included. The primary outcome was pCR, defined as ypT0N0. A meta-analysis of studies comparing an intervention with standard fluoropyrimidine-based chemoradiation (CRT) was performed. Results Of the 17 articles included in the systematic review, 11 were used for the meta-analysis. Addition of oxaliplatin to fluoropyrimidine-based CRT resulted in significantly more pCR compared with fluoropyrimidine-based CRT only (OR 1.46), but at the expense of more ≥ grade 3 toxicity. Other treatment strategies, including consolidation/induction chemotherapy and short-course radiotherapy (SCRT), did not improve pCR rates. None of the included trials reported a benefit in local control or OS. Five-year DFS was significantly worse after SCRT-delay compared with CRT (59% vs. 75.1%, HR 1.93). Conclusions All included trials fail to deliver high-level evidence to show an improvement in pCR compared with standard fluoropyrimidine-based CRT. The addition of oxaliplatin might result in more pCR but at the expense of more toxicity. Furthermore, this benefit does not translate into less local recurrence or improved survival.

Residual rectal cancer after preoperative radiochemotherapy (ypT1-2): An indication for local excision instead of radical surgery?

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 546-546
Author(s):  
Thilo Sprenger ◽  
Hilka Rothe ◽  
Lena-Christin Conradi ◽  
Kia Homayounfar ◽  
Tim Beissbarth ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Excision ◽  
Bowel Wall ◽  
Radical Surgery ◽  
Pathologic Complete Response ◽  
Residual Tumor ◽  
Complete Response ◽  
Phase Iii ◽  
Preoperative Radiochemotherapy ◽  
Cancer Trial

546 Background: Preoperative radiochemotherapy (RCT) followed by total mesorectal excision (TME) has improved local tumor control and led to a significant tumor downstaging. For patients with pathologic complete response (ypT0) as well as residual tumor restricted only to the bowel wall (ypT1-2) local excision has increasingly been discussed to avoid significant morbidity and functional deficits associated with TME. Therefore we investigated the incidence, distribution and tumor-related localization of mesorectal lymph node (LN) metastases in TME specimens with ypT0, ypT1-2 and ypT3-4 rectal cancers, respectively. Methods: TME specimens from 81 patients with locally advanced rectal cancer treated with neoadjuvant RCT within the phase III German Rectal Cancer Trial CAO/ARO/AIO-04 were evaluated. The entire mesorectal compartment was screened microscopically after complete paraffin embedding. The number and localization of all detectable LN metastases was specified in relation to the primary tumor. Results: Whereas 50 patients (62%) had ypT3-4 carcinomas after neoadjuvant RCT 20 patients (25%) presented with residual tumor within the bowel wall (ypT1-2). 11 patients (14%) had pathologic complete response (ypT0). 28 ± 13.7 LN were detected per specimen. 25 patients (31%) had residual LN metastases after RCT. Although the incidence was higher in the ypT3-4 group (40% ypN+) still 25% of patients in the ypT1-2 group had a mean number of 2.2 residual LN metastases. 55% of these metastases were located afar from the primary lesion in the proximal mesorectum. No patient with ypT0 status had residual LN metastases. Conclusions: Even in patients with good response and tumors restricted only to the bowel wall (ypT1-2) after RCT there is a considerable risk for residual LN metastases. The majority of metastases were located clearly outside the tumor region. Local excision of residual rectal cancer would be accompanied by a higher rate of local failure and radical surgery with TME should remain the standard treatment in those patients.

Rectal adenocarcinoma: Outcomes of adjuvant chemotherapy after neoajuvant chemoradiotherapy in a retrospective cohort.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 790-790
Author(s):  
Vanessa Pachón Olmos ◽  
Pablo Reguera Puertas ◽  
Reyes Ferreiro Monteagudo ◽  
FEDERICO LONGO ◽  
Mercedes Rodríguez Garrote ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Rectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Complete Response ◽  
Local Relapse ◽  
Stage Ii ◽  
Systemic Relapse ◽  
The Impact

790 Background: The role of adjuvant chemotherapy (AC) after chemoradiotherapy and surgery in stage II and III of rectal cancer is not well defined. Neither the regimen nor the duration is clear. Besides, guidelines from different expert groups are conflicting. Methods: 224 patients diagnosed from January 2003 to December 2013 with rectal adenocarcinoma T3/T4 and/or positive node staged by ultrasound or magnetic resonance imaging was collected retrospectively from the Pathology Department data base. Results: Of the 224 patients 61.6% were male, median of age at diagnosis 68.6 years (range 31.3-85.4). All of them received 50.4 Gy with different concomitant regimens (capecitabine, continuous infusion of fluoracil or bolus of fluoracil-leucovorin). 13.4% of patients achieved a pathological complete response. 76.8% of the cohort received adjuvant chemotherapy. The main reasons for not receiving chemotherapy were ECOG ≥ 2, surgery complications and a decision of the patient. 51.2% of patients received an oxaliplatin based regimen and the median time of chemotherapy duration was 4 months (range 1-6 months). Local relapse was diagnosed in 6.3% of patients while a systemic relapse was found in 22.3%. Patients without AC had a mean overall survival (OS) of 85.5 months (CI 95% 70.7-100.4) versus 119.8 monts (CI 95% 110.8-128.8) in the AC cohort (p 0.002) without reaching the median after 58 months (range 8-153.9) median follow-up. Disease free survival (DFS) was also better in the AC cohort with a mean DFS of 104 months (CI 95% 94.3-113.6) versus 71.4 months (CI 95% 55.4-87.4), p = 0.01. Conclusions: AC after chemoradiotherapy and surgery in stage II and III rectal cancer as a standard does not exist. In our cohort, AC showed a significant improve in OS and DFS, but the limitations of a retrospective study should be considered, as well as the impact of surgery on metastasis and salvage chemotherapies. Randomized studies are clearly needed.

Planned organ preservation for selected T2-3 rectal cancer: French experience using chemoradiotherapy and contact xray boost.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 751-751
Author(s):  
Jean-Pierre Gerard ◽  
Nicolas N. Barbet ◽  
Catherine Dejean ◽  
Ludovic Evesque ◽  
Karine Benezery ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Local Excision ◽  
Organ Preservation ◽  
Cell Cancer ◽  
Bowel Function ◽  
Complete Response ◽  
Local Relapse ◽  
Tumor Diameter ◽  
Clinical Complete Response ◽  
French Experience

751 Background: The Lyon R96-02 randomized trial has demonstrated in T2-3 rectal cancer that external beam radiotherapy (EBRT) with Contact X Ray brachytherapy (CXB) boost was increasing clinical complete response, sphincter preservation and in early cases organ preservation. We report French experience in 3 radiotherapy departments using CXB boost with chemoradiotherapy (CRT) in early T2T3N0. Methods: Selection based on digital rectal examination, colonoscopy, MRI (and/or Endorectal-ultrasound). Inclusion : adenocarcinoma (distal, middle rectum), T2 T3a-b, tumor diameter ≤ 4cm, N0, M0. Treatment : CXB (80-110 Gy/3-4 fr) followed by CRT (CAP 50). Tumor response assess on week 14 : DRE, rigid rectoscopy and MRI. Clinical complete response (cCR) defined as no visible tumor, supple rectal wall and TRG 1-2 on MRI. In case of cCR a close surveillance or local excision was proposed. Results: Between 2002 -2016, 84 patients treated. Median age: 75 years, Male: 59, Female: 25. Operable patients: 69 (83%). T2 : 52, T3 : 32 (Lyon Villeurbanne : 16, Macon : 11, Nice : 57). Median follow-up time : 53 months. cCR was achieved in 94% of cases. Local excision performed in 17 patients (ypT0 : 16). At 4 years, the cancer specific survival was 82% [CI:96-70] and the local relapse rate 12% [CI: 2-22]. No isolated perirectal lymph node relapse observed. After 4 years, 3 more local relapses observed (4, 6, 7 years). Main late toxicity ( > 6 months after treatment) was rectal bleeding (radiation telangiectasia) which required plasma argon coagulation in 5 patients. No TME surgery was performed and organ preservation was achieved in all cases. Bowel function was good in 85% of patients (LARS score < 20). Conclusions: When combining CXB with CRT, rectal cancer T2T3a-b N0 ≤4cm achieve a high rate of cCR (≥85%) with organ preservation, good bowel function, low rate of local relapse ( < 15%) and low toxicity. As rectal adenocarcinoma is radioresistant, the treatment must use a CXB boost. Like anal squamous cell cancer, planned organ preservation can be proposed to operable patients. The ongoing European OPERA trial aims at bringing evidence to this option.

Sign in / Sign up

Export Citation Format

Share Document