Diagnostic accuracy of MRI in assessing tumor regression and identifying complete response in patients with locally advanced rectal cancer after neoadjuvant treatment

2018 ◽  
Vol 43 (12) ◽  
pp. 3213-3219 ◽  
Author(s):  
Medhat Aker ◽  
Darren Boone ◽  
Anuradha Chandramohan ◽  
Bruce Sizer ◽  
Roger Motson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Diagnostic Accuracy ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

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.

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 .

Deferral of rectal surgery following a continued response to preoperative chemoradiotherapy (Watch and Wait) study: A phase II multicenter study in the United Kingdom.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 489-489 ◽  
Author(s):  
S. K. Yu ◽  
G. Brown ◽  
R. J. Heald ◽  
S. Chua ◽  
G. Cook ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Resection ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Staging ◽  
Pet Ct

489 Background: Neoadjuvant chemoradiotherapy (CRT) and surgical resection are standard components of therapy for patients locally advanced rectal cancer (T3,T4 or N+) in UK. In 15%-30% of patients treated pre-operatively with CRT will develop pathological complete response (CR). The time from completion of CRT to maximal tumour response is as yet unknown. This study is the first prospective study to attempt to identify the percentage of patients who can safely omit surgery and the safety of deferred surgery in patients who achieve clinical complete response post CRT. Of the 59 patients required for the study, this provides an update on 19 patients entered. Methods: Patients with locally advanced rectal cancer requiring neoadjuvant treatment are identified in the multidisciplinary meet (MDT). Patients undergo CRT using a minimum of 50.4Gy in 28 # daily conformal CT planned CRT with concomitant Capecitabine at 825mg/m2 BD. MRI pelvis and body CT are repeated 4 weeks post CRT and rediscussed at MDT. If there is a good partial response or CR, patients are considered for Deferral of Surgery Study. Based on the pre treatment clinical staging, patients are considered for adjuvant chemotherapy as per NICE guidance. At any point of the study, if there is histology proven tumour regrowth or progression, patient undergo surgery. Results: 10 (53%) patients remain in CR. 6 (32%) patients underwent surgical resection with clear margin after detection of tumour regrowth at from 2-23 months post CRT. 5 out of 6 of the patients with tumour regrowth underwent PET CT as per protocol, and all tumour regrowth in those 5 patients were detected by PET CT, i.e. FDG avid disease. The pathological stages on these 6 patients were ypT2N0 CRM negative in 5 and ypT3N0 CRM negative in 1. 3 (15%) patients with tumour regrowth refused surgery. Conclusions: In the 19 recruited patients, all the patients with tumour regrowth underwent surgical resection with clear margins. PET CT appears a useful tool for detecting tumour regrowth. The median time for tumour regrowth is 17.5 months post CRT. The trial will be successful if at least 11/59 patients are able to safely omit surgery. Accrual of patients continues. No significant financial relationships to disclose.

scholarly journals Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer

2021 ◽  
Vol 28 (1) ◽  
pp. 283-293
Author(s):  
Zhiwei Zhai ◽  
Kunning Zhang ◽  
Chen Wang ◽  
Tian Zhang ◽  
Lixia Wang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Distant Metastases ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Consolidation Chemotherapy ◽  
Significant Difference

Background and Objectives: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. Methods: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. Results: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. Conclusions: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.

scholarly journals Pre-Treatment T2-WI Based Radiomics Features for Prediction of Locally Advanced Rectal Cancer Non-Response to Neoadjuvant Chemoradiotherapy: A Preliminary Study

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1894 ◽  
Author(s):  
Bianca Petresc ◽  
Andrei Lebovici ◽  
Cosmin Caraiani ◽  
Diana Sorina Feier ◽  
Florin Graur ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Imaging Biomarkers ◽  
Tumor Regression Grade ◽  
Pre Treatment

Locally advanced rectal cancer (LARC) response to neoadjuvant chemoradiotherapy (nCRT) is very heterogeneous and up to 30% of patients are considered non-responders, presenting no tumor regression after nCRT. This study aimed to determine the ability of pre-treatment T2-weighted based radiomics features to predict LARC non-responders. A total of 67 LARC patients who underwent a pre-treatment MRI followed by nCRT and total mesorectal excision were assigned into training (n = 44) and validation (n = 23) groups. In both datasets, the patients were categorized according to the Ryan tumor regression grade (TRG) system into non-responders (TRG = 3) and responders (TRG 1 and 2). We extracted 960 radiomic features/patient from pre-treatment T2-weighted images. After a three-step feature selection process, including LASSO regression analysis, we built a radiomics score with seven radiomics features. This score was significantly higher among non-responders in both training and validation sets (p < 0.001 and p = 0.03) and it showed good predictive performance for LARC non-response, achieving an area under the curve (AUC) = 0.94 (95% CI: 0.82–0.99) in the training set and AUC = 0.80 (95% CI: 0.58–0.94) in the validation group. The multivariate analysis identified the radiomics score as an independent predictor for the tumor non-response (OR = 6.52, 95% CI: 1.87–22.72). Our results indicate that MRI radiomics features could be considered as potential imaging biomarkers for early prediction of LARC non-response to neoadjuvant treatment.

scholarly journals Neoadjuvant treatment (FOLFOX4 plus hypofractionated tomotherapy) for patients with locally advanced rectal cancer: a multicenter phase II trial

2020 ◽  
Vol 12 ◽  
pp. 175883592097713
Author(s):  
Alessandro Passardi ◽  
Ilario Giovanni Rapposelli ◽  
Emanuela Scarpi ◽  
Elisa Neri ◽  
Elisabetta Parisi ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Target Volume ◽  
Locally Advanced Rectal Cancer ◽  
Common Grade ◽  
Grade 3 ◽  
Registration Date

Aims: This study aims to evaluate the safety and efficacy of a new neoadjuvant regimen (FOLFOX4 plus hypofractionated tomotherapy) in patients with locally advanced rectal cancer. Methods: Patients with stage II–III rectal cancer were treated with the pre-operative chemoradiotherapy regimen comprising FOLFOX4 (two cycles), TomoTherapy (25 Gy in five consecutive fractions, one fraction per day in 5 days on the clinical target volume at the isodose of 95% of the total dose), FOLFOX4 (two cycles), followed by surgery with total mesorectal excision and adjuvant chemotherapy with FOLFOX4 (eight cycles). The primary endpoint was pathological complete response (pCR). Results: Fifty-two patients were enrolled and 50 patients were evaluable. A total of 46 (92%) patients completed chemoradiotherapy according to the study protocol and 49 patients underwent surgery. Overall, 12 patients achieved a pCR (24.5%, 95% CI 12.5–36.5). The most common grade 3 or more adverse events were neutropenia and alteration of the alvus. Adverse reactions due to radiotherapy, mainly grade 1–2 dermatitis, tenesmus, urinary dysfunction and pain, were tolerable and fully reversible. The most important surgical complications included infection, anastomotic leakage and fistula, all resolved with conservative treatment. Conclusion: FOLFOX and hypofractionated TomoTherapy is effective and safe in patients with locally advanced rectal cancer. Long-term efficacy needs to be further evaluated. Trial registration ClinicalTrials.gov identifier: NCT02000050 (registration date: 26 November 2013) https://clinicaltrials.gov/ct2/show/NCT02000050

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