scholarly journals Can Pre-Treatment Inflammatory Parameters Predict the Probability of Sphincter-Preserving Surgery in Patients with Locally Advanced Low-Lying Rectal Cancer?

Diagnostics ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 946
Author(s):  
Richard Partl ◽  
Katarzyna Lukasiak ◽  
Bettina Stranz ◽  
Eva Hassler ◽  
Marton Magyar ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Anal Verge ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Sphincter Preservation ◽  
Independent Predictive Factor ◽  
Lymphocyte Ratio ◽  
Inflammatory Parameters ◽  
Pre Treatment

There is evidence suggesting that pre-treatment clinical parameters can predict the probability of sphincter-preserving surgery in rectal cancer; however, to date, data on the predictive role of inflammatory parameters on the sphincter-preservation rate are not available. The aim of the present cohort study was to investigate the association between inflammation-based parameters and the sphincter-preserving surgery rate in patients with low-lying locally advanced rectal cancer (LARC). A total of 848 patients with LARC undergoing radiotherapy from 2004 to 2019 were retrospectively reviewed in order to identify patients with rectal cancer localized ≤ 6 cm from the anal verge, treated with neo-adjuvant radiochemotherapy (nRCT) and subsequent surgery. Univariable and multivariable analyses were used to investigate the role of pre-treatment inflammatory parameters, including the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for the prediction of sphincter preservation. A total of 363 patients met the inclusion criteria; among them, 210 patients (57.9%) underwent sphincter-preserving surgery, and in 153 patients (42.1%), an abdominoperineal rectum resection was performed. Univariable analysis showed a significant association of the pre-treatment CRP value (OR = 2.548, 95% CI: 1.584–4.097, p < 0.001) with sphincter preservation, whereas the pre-treatment NLR (OR = 1.098, 95% CI: 0.976–1.235, p = 0.120) and PLR (OR = 1.002, 95% CI: 1.000–1.005, p = 0.062) were not significantly associated with the type of surgery. In multivariable analysis, the pre-treatment CRP value (OR = 2.544; 95% CI: 1.314–4.926; p = 0.006) was identified as an independent predictive factor for sphincter-preserving surgery. The findings of the present study suggest that the pre-treatment CRP value represents an independent parameter predicting the probability of sphincter-preserving surgery in patients with low-lying LARC.

Multi-institutional assessment of sphincter preservation for rectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 566-566
Author(s):  
Zaid M. Abdelsattar ◽  
Sandra L. Wong ◽  
Nancy J. Birkmeyer ◽  
Robert K. Cleary ◽  
Melissa L. Times ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Selection Criteria ◽  
Clinical Characteristics ◽  
Anal Verge ◽  
Multivariable Analysis ◽  
Hospital Performance ◽  
Sphincter Preservation ◽  
Case Mix ◽  
General Hypothesis ◽  
Hospital Variation

566 Background: Rates of sphincter preserving surgery (SPS) have been proposed as a quality measure for rectal cancer (RC) surgery. However, administrative and registry-based SPS rates often lack critical patient and tumor characteristics, rendering it unclear if variations in SPS rates are due to unmeasured case-mix differences or selection criteria. The aim of this study was to determine whether hospitals’ SPS rates differ after accounting for clinical characteristics. Methods: As part of a RC quality project, 10 hospitals in the Michigan Surgical Quality Collaborative retrospectively collected RC-specific data from 2007-2012. We assessed for SPS predictors using multivariable regression. Patients were categorized as “definitely SPS eligible” a priori if they did not have any of the following: poor sphincter control, stoma preference, sphincter involvement, tumor <6 cm from the anal verge (an intentionally conservative cutoff) or metastatic disease. We compared hospital performance with and without these clinical data using Spearman’s correlations. Results: In total, 349 patients underwent surgery for RC in 10 hospitals (5/10 high volume and 6/10 major teaching). Of those, 74% had SPS (range by hospital 50%-91%). On multivariable analysis, only pre-op radiation, tumor location, hospital teaching status and hospital ID were independent predictors of SPS, but not age, sex, BMI, AJCC stage, ASA class, or hospital CRC surgery volume. Analyses of the “definitely eligible” patients revealed an overall SPS rate of 88% (65-100%). Hospital SPS rankings using crude versus clinically-adjusted SPS rates proved to be highly correlated (Spearman’s ρ= 0.9). Tumor locations suggest differing selection criteria for SPS in different hospitals (Table). Conclusions: Rates of SPS vary by hospital, even after correcting for clinical characteristics using detailed chart review. These data suggest missed opportunities for SPS, and refute the general hypothesis that hospital variation in SPS rates in previous studies is due to unmeasured case-mix differences. [Table: see text]

Neoadjuvant cetuximab, capecitabine, and radiotherapy (RT) in locally advanced resectable rectal cancer: results of a phase II trial

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15029-e15029
Author(s):  
V. Velenik ◽  
J. Ocvirk ◽  
I. Oblak ◽  
F. Anderluh
Keyword(s):  
Rectal Cancer ◽  
Phase Ii ◽  
Tumor Regression ◽  
Anal Verge ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Sphincter Preservation ◽  
Open Label ◽  
Resectable Rectal Cancer ◽  
Grade 3

e15029 Background: Preoperative chemoradiotherapy (CRT) with capecitabine is a treatment of choice for locally advanced rectal cancer. The radiosensitizing effect of cetuximab, an EGFR-targeting monoclonal antibody, may further enhance the tumor response. The aim of this prospective, nonrandomized, open-label phase II study was to establish the efficacy and safety profile of cetuximab combined with capecitabine and concurrent RT for locally advanced resectable rectal cancer. Methods: Patients (pts) with stage II or III rectal cancer confirmed by MRI were treated with capecitabine 1250 mg/m2 twice daily for 2 weeks. Cetuximab 400mg/m2 was intravenously administered on week 3, followed by cetuximab 250mg/m2/week and capecitabine 825 mg/m2 bid including weekends during RT. The RT dose was 45 Gy (25×1.8 Gy, 3D conformal technique), starting on week 4. Total mesorectal excision was scheduled 4–6 weeks after completion of CRT. Tumor regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was complete pathologic response (pCR). Results: Thirty-seven pts were eligible for safety and efficacy analyses. Median age was 55 (range: 33–72) years, 81% of pts were male. Three pts (8.1%) had T3N0 tumors, 1 pt (2.7%) T2N1, 13 pts (35%) T3N1, 1 pt (2.7%) T2N2, 15 pts (40.5%) T3N2 and 4 pts (11%) T4N2. The median tumor distance from anal verge was 6 (range: 1–11) cm. All pts received 45 Gy RT. Dose reduction/treatment interruption was necessary for 9/37 (24.3%) pts owing to hypersensitivity reaction (n=4), hepatotoxicity grade 3 (n=1) or diarrhea grade 3 (n=4). Other grade 3 toxicities included dermatitis (n=6, 16.2%), anorexia (n=1, 2.7%) and infection (n=1, 2.7%). TRG 4 (pCR) was recorded in 3 pts (8.1%) and TRG 3 in 7 pts (18.9%). T-, N- and overall downstaging rates were 56.8%, 81.1% and 73.0%, respectively. The total sphincter preservation rate was 75.7%; in 17 pts whose tumors were located ≤5 cm of the anal verge, the rate was 53%. Conclusions: Preoperative CRT with cetuximab and capecitabine is safe and feasible. A high pathologic downstaging rate was achieved, although the pCR rate appeared to be in the range previously reported for CRT with capecitabine. No significant financial relationships to disclose.

A phase II clinical trial platform for sensitization testing using total neoadjuvant therapy (TNT) in rectal cancer: Nrg-GI002.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. TPS721-TPS721
Author(s):  
Thomas J. George ◽  
Greg Yothers ◽  
Osama E. Rahma ◽  
Theodore S. Hong ◽  
Marcia McGory Russell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Rectal Cancer ◽  
High Risk ◽  
Surgical Resection ◽  
Phase Ii ◽  
Anal Verge ◽  
Locally Advanced ◽  
High Risk Patient ◽  
Sphincter Preservation ◽  
Sphincter Function

TPS721 Background: Locally advanced rectal cancer (LARC) improvements have plateaued due to an inability to consistently deliver adjuvant therapy and effective novel therapies. Systematic testing of new chemotherapy and radiation sensitizers is needed to advance treatment outcomes. This NCTN multi-arm randomized phase II modular clinical trial platform utilizes TNT with parallel experimental arms (EA) in LARC. The EAs are not intended for direct comparison, but rather to test a variety of sensitizers or hypotheses in a consistent and homogenous high-risk patient (pt) population with correlative biomarkers. Success of any EA will be determined by achievement of pathologic endpoints compared to a control arm. Methods: The NRG-GI002 trial serves as a modular platform to assess novel sensitizers to neoadjuvant chemotherapy and/or chemoradiotherapy (chemoRT) in LARC. Eligibility includes LARC with any ONE of the following: distal location (cT3-4 ≤ 5 cm from anal verge, any N); bulky (any cT4 or tumor within 3 mm of the mesorectal fascia); high risk for metastatic disease (cN2); or not a candidate for sphincter-sparing surgical resection. After randomization, pts receive neoadjuvant FOLFOX x 4 mo→chemoRT (capecitabine with 50.4 Gy)→surgical resection 8-12 wks later. The first EA will assess activity of veliparib with standard chemoRT. Enrollment to this EA is complete (results anticipated late 2019). The second EA, testing pembrolizumab concurrently with and following chemoRT, is currently active, with several other EAs in development. Primary endpoint is demonstrated improvement in Neoadjuvant Rectal Cancer score for the EA v control representing a 20% relative risk reduction in DFS HR and 3-4% absolute OS improvement. Secondary endpoints include comparisons of OS, DFS, toxicity, pCR, cCR, therapy completion, negative surgical margins, sphincter preservation, sphincter function including QOL, and exploratory assessments of molecular and radiographic predictors of response and distant failure. Target accrual is 79 evaluable pts/arm with additional EAs added through protocol amendments. NCT02921256. Support: U10CA180868, -180822, UG1-189867, U24-196067; AbbVie, Merck. Clinical trial information: NCT02921256.

scholarly journals Clinical parameters predictive for sphincter-preserving surgery and prognostic outcome in patients with locally advanced low rectal cancer

2020 ◽  
Author(s):  
Richard Partl ◽  
Marton Magyar ◽  
Eva Hassler ◽  
Tanja Langsenlehner ◽  
Karin Sigrid Kapp
Keyword(s):  
Rectal Cancer ◽  
Karnofsky Performance Status ◽  
Anal Verge ◽  
Performance Status ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Sphincter Preservation ◽  
Low Rectal Cancer ◽  
Clinical Parameters ◽  
Histopathological Response

Abstract Background Although controversial, there are data suggesting that clinical parameters can predict the probability of sphincter preserving procedures in rectal cancer. The purpose of this study was to investigate the association between clinical parameters and the sphincter-preserving surgery rate in patients who had undergone neoadjuvant combination therapy for advanced low rectal cancer. Methods In this single center study, the charts of 540 patients with locally advanced rectal cancer who had been treated with induction chemotherapy-and/or neoadjuvant concomitant radiochemotherapy (nRCT) over an 11-year period were reviewed in order to identify patients with rectal cancer ≤6 cm from the anal verge, who had received the prescribed nRCT only. Univariate and multivariate analyses were used to identify pretreatment patient- and tumor associated parameters correlating with sphincter preservation. Survival rates were calculated using Kaplan-Meier analyses. Results 280 of the 540 patients met the selection criteria. Of the 280 patients included in the study, 158 (56.4%) underwent sphincter-preserving surgery. 164 of 280 patients (58.6%) had a downsizing of the primary tumor (ypT < cT) and 39 (23.8%) of these showed a complete histopathological response (ypT0 ypN0). In univariate analysis, age prior to treatment, Karnofsky performance status, clinical T-size, relative lymphocyte value, CRP value, and interval between nRCT and surgery, were significantly associated with sphincter-preserving surgery. In multivariate analysis, age (hazard ratio (HR)=1.05, CI95%: 1.02-1.09, p=0.003), relative lymphocyte value (HR=0.94, CI95%: 0.89-0.99, p=0.029), and interval between nRCT and surgery (HR=2.39, CI95%: 1.17-4.88, p=0.016) remained as independent predictive parameters. A significant longer disease-free (p =0.009) and overall survival (p =0.004) were observed in the sphincter-preserving surgery group. Conclusions The findings of our study in a consistently treated cohort of 280 patients with advanced low rectal cancer suggest that clinical parameters have a role in predicting sphincter-preserving surgery.

scholarly journals Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD

2021 ◽  
Vol 39 (1) ◽  
pp. 17-29 ◽  
Author(s):  
Hans-Joachim Schmoll ◽  
Alexander Stein ◽  
Eric Van Cutsem ◽  
Timothy Price ◽  
Ralf D. Hofheinz ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Anal Verge ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Rectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Site Location ◽  
Intention To Treat

PURPOSE The PETACC 6 trial investigates whether the addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative capecitabine improves disease-free survival (DFS) in locally advanced rectal cancer. METHODS Between November 2008 and September 2011, patients with rectal adenocarcinoma within 12 cm from the anal verge, T3/4 and/or node positive, were randomly assigned to 5 weeks preoperative capecitabine-based chemoradiation (45-50.4 Gy) followed by six cycles of adjuvant capecitabine, both without (control arm, 1) or with (experimental arm, 2) oxaliplatin. The primary end point was improvement of 3-year DFS by oxaliplatin from 65% to 72% (hazard ratio [HR], 0.763). RESULTS A total of 1,094 patients were randomly assigned (intention to treat), and 1,068 eligible patients started their allocated treatment (arm 1, 543; arm 2, 525), with completion of protocol treatment in 68% (arm 1) v 54% (arm 2). A higher rate of grade 3/4 adverse events was reported in the experimental arm (14.4% v 37.3% and 23.4% v 46.6% for neoadjuvant and adjuvant treatment, respectively). At a median follow-up of 68 months (interquartile range, 58-74 months), 157 and 156 DFS events were observed in arms 1 and 2, respectively (adjusted HR, 1.02; 95% CI, 0.82 to 1.28; P = .835). Three-year DFS rate was not different, with 76.5% (95% CI, 72.7% to 79.9%) in arm 1, which is higher than anticipated, and 75.8% (95% CI, 71.9% to 79.3%) in arm 2. The 7-year DFS and overall survival (OS) rates were not different as well, with DFS of 66.1% v 65.5% (HR, 1.02) and OS of 73.5% v 73.7% (HR, 1.19) in arms 1 and 2, respectively. Subgroup analyses revealed heterogeneity in treatment effect according to German versus non-German site location, without detectable confounding factors in multivariable analysis. CONCLUSION The addition of oxaliplatin to preoperative capecitabine-based chemoradiation and postoperative adjuvant chemotherapy impairs tolerability and feasibility and does not improve efficacy.

Institutional variation in the thoroughness of pathologic assessment and pathologic complete response rates for locally advanced rectal cancers treated with neoadjuvant chemoradiation.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 696-696
Author(s):  
Oliver S Chow ◽  
Sujata Patil ◽  
Metin Keskin ◽  
Jesse Joshua Smith ◽  
Maria Widmar ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Size ◽  
Anal Verge ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Residual Tumor ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Pathologic Assessment

696 Background: A pathologic complete response (pCR) after neoadjuvant therapy and surgical excision is associated with a better prognosis and guides the management of patients with locally advanced rectal cancer. It is not known whether the thoroughness of pathologic assessment correlates with the finding of pCR. Methods: We introduce a surrogate measure for the thoroughness of pathologic assessment by taking the ratio of maximum residual tumor size and the number of cassettes prepared from the tumor: the Tumor Size to Cassette Ratio (TSCR). We retrospectively reviewed pathology reports from 259 patients with Stage II/III rectal cancer enrolled in a multicenter prospective clinical trial to determine whether TSCR is associated with pCR. Results: Of 247 included patients, 71 (29%) had a pCR. The pCR rate ranged from 0-45% and TSCR ranged from 0.0004 to 1.67 across the twelve trial sites. TSCR was significantly associated with pCR on univariable analysis. On multivariable analysis, TSCR remained significantly associated with pCR (odds ratio of 0.05; 95% CI 0.008-0.302) after adjusting for clinical stage, tumor size, distance from anal verge, radiation dose, and the number of neoadjuvant cycles of FOLFOX received. Conclusions: Pathologists tend to assess rectal cancer specimens with a pCR more thoroughly, but the thoroughness of pathologic assessment of residual tumor specimens varies between institutions. The thoroughness of pathologic assessment is associated with pCR. This raises the need for further standardization in the assessment of rectal cancer specimens after neoadjuvant chemoradiation.

scholarly journals MRI-based clinical-radiomics model predicts tumor response before treatment in locally advanced rectal cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Andrea Delli Pizzi ◽  
Antonio Maria Chiarelli ◽  
Piero Chiacchiaretta ◽  
Martina d’Annibale ◽  
Pierpaolo Croce ◽  
...  
Keyword(s):  
Machine Learning ◽  
Rectal Cancer ◽  
Treatment Response ◽  
Randomized Clinical Trials ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Learning Model ◽  
Partial Least Square ◽  
Machine Learning Model ◽  
Pre Treatment

AbstractNeoadjuvant chemo-radiotherapy (CRT) followed by total mesorectal excision (TME) represents the standard treatment for patients with locally advanced (≥ T3 or N+) rectal cancer (LARC). Approximately 15% of patients with LARC shows a complete response after CRT. The use of pre-treatment MRI as predictive biomarker could help to increase the chance of organ preservation by tailoring the neoadjuvant treatment. We present a novel machine learning model combining pre-treatment MRI-based clinical and radiomic features for the early prediction of treatment response in LARC patients. MRI scans (3.0 T, T2-weighted) of 72 patients with LARC were included. Two readers independently segmented each tumor. Radiomic features were extracted from both the “tumor core” (TC) and the “tumor border” (TB). Partial least square (PLS) regression was used as the multivariate, machine learning, algorithm of choice and leave-one-out nested cross-validation was used to optimize hyperparameters of the PLS. The MRI-Based “clinical-radiomic” machine learning model properly predicted the treatment response (AUC = 0.793, p = 5.6 × 10–5). Importantly, the prediction improved when combining MRI-based clinical features and radiomic features, the latter extracted from both TC and TB. Prospective validation studies in randomized clinical trials are warranted to better define the role of radiomics in the development of rectal cancer precision medicine.

scholarly journals Retrospective study of the functional and oncological outcomes of conformal sphincter preservation operation in the treatment of very low rectal cancer

2020 ◽  
Vol 24 (10) ◽  
pp. 1025-1034 ◽  
Author(s):  
G. Sun ◽  
Z. Lou ◽  
H. Zhang ◽  
G. Y. Yu ◽  
K. Zheng ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Rectal Wall ◽  
Anal Verge ◽  
Disease Free Survival ◽  
Sphincter Preservation ◽  
Low Rectal Cancer ◽  
Anal Function ◽  
Oncological Outcomes ◽  
Rectal Cancers ◽  
Very Low Rectal Cancer

Abstract Background Conformal sphincter preservation operation (CSPO) is a new surgical procedure for very low rectal cancers (within 4–5 cm from the anal verge). CSPO preserves more of the dentate line and distal rectal wall and also avoids injuring nerves in the intersphincteric space, resulting in satisfactory anal function after resection. The aim of this study was to analyze the short-term surgical results and long-term oncological and functional outcomes of CSPO. Methods Consecutive patients with very low rectal cancer, who had CSPO between January 2011 and October 2018 at Changhai Hospital, Shanghai were included. Patient demographics, clinicopathological features, oncological outcomes and anal function were analyzed. Results A total of 102 patients (67 men) with a mean age of 56.9 ± 10.8 years were included. The median distance of the tumor from the anal verge was 3 (IQR, 3–4) cm. Thirty-five patients received neoadjuvant chemoradiation (nCRT). The median distal resection margin (DRM) was 0.5 (IQR, 0.3–0.8) cm. One patient had a positive DRM. All circumferential margins were negative. There was no perioperative mortality. The postoperative complication rate was 19.6%. The median duration of follow-up was 28 (IQR, 12–45.5) months. The local recurrence rate was 2% and distant metastasis rate was 10.8%. The 3-year overall survival and disease-free survival rates were 100% and 83.9%, respectively. The mean Wexner incontinence and low anterior resection syndrome scores 12 months after ileostomy reversal were 5.9 ± 4.3, and 29.2 ± 6.9, respectively. Conclusions For patients with very low rectal cancers, fecal continence can be preserved with CSPO without compromising oncological results.

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