scholarly journals Vascular calcification and response to neoadjuvant therapy in locally advanced rectal cancer: an exploratory study

2021 ◽  
Author(s):  
Katrina A. Knight ◽  
Ioanna Drami ◽  
Donald C. McMillan ◽  
Paul G. Horgan ◽  
James H. Park ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Poor Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tumour Regression ◽  
Royal Infirmary

Abstract Purpose Patients with locally advanced rectal cancer (LARC) may experience a clinical complete response (cCR) to neoadjuvant chemoradiotherapy (NACRT) and opt for non-operative management. Pathological factors that relate to NACRT response have been well described. Host factors associated with response, however, are poorly defined. Calcification of the aortoiliac (AC) vessels supplying the rectum may influence treatment response. Methods Patients with LARC having NACRT prior to curative surgery at Glasgow Royal Infirmary (GRI) and St Mark’s hospital (SMH) between 2008 and 2016 were identified. AC was scored on pre-treatment CT imaging. NACRT response was assessed using pathologic complete response (pCR) rates, tumour regression grades (TRGs), the NeoAdjuvant Rectal score and T-/N-downstaging. Associations were assessed using Chi-squared, Mantel–Haenszel and Fisher’s exact tests. Results Of 231 patients from GRI, 79 (34%) underwent NACRT for LARC. Most were male (58%), aged over 65 (51%) with mid- to upper rectal tumours (56%) and clinical T3/4 (95%), node-positive (77%) disease. pCR occurred in 10 patients (13%). Trends were noted between higher clinical T stage and poor response by Royal College of Pathologist’s TRG (p = 0.021) and tumour height > 5 cm and poor response by Mandard TRG (0.068). In the SMH cohort, 49 of 333 (15%) patients underwent NACRT; 8 (16%) developed a pCR. AC was not associated with NACRT response in either cohort. Conclusions AC was not associated with NACRT response in this cohort. Larger contemporary cohorts are required to better assess host determinants of NACRT response and develop predictive models to improve patient selection.

Phase Ib/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib ◽  
Grade 3

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]

scholarly journals Avoiding Unnecessary Major Rectal Cancer Surgery by Implementing Structural Restaging and a Watch-and-Wait Strategy After Neoadjuvant Radiochemotherapy

2020 ◽  
Author(s):  
J. F. Huisman ◽  
I. J. H. Schoenaker ◽  
R. M. Brohet ◽  
O. Reerink ◽  
H. van der Sluis ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Response Evaluation ◽  
Watch And Wait ◽  
Time To Event

Abstract Background Pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) is found in 15–20% of patients with locally advanced rectal cancer. A watch-and-wait (W&W) strategy has been introduced as an alternative strategy to avoid surgery for selected patients with a clinical complete response at multidisciplinary response evaluation. The primary aim of this study was to evaluate the efficacy of the multidisciplinary response evaluation by comparing the proportion of patients with pCR since the introduction of the structural response evaluation with the period before response evaluation. Methods This retrospective cohort study enrolled patients with locally advanced rectal cancer who underwent nCRT between January 2009 and May 2018, categorizing them into cohort A (period 2009–2015) and cohort B (period 2015–2018). The patients in cohort B underwent structural multidisciplinary response evaluation with the option of the W&W strategy. Proportion of pCR (ypT0N0), time-to-event (pCR) analysis, and stoma-free survival were evaluated in both cohorts. Results Of the 259 patients in the study, 21 (18.4%) in cohort A and in 8 (8.7%) in cohort B had pCR (p = 0.043). Time-to-event analysis demonstrated a significant pCR decline in cohort B (p < 0.001). The stoma-free patient rate was 24% higher in cohort B (p < 0.001). Conclusion Multidisciplinary clinical response evaluation after nCRT for locally advanced rectal cancer led to a significant decrease in unnecessary surgery for the patients with a complete response.

scholarly journals Predictors of Pathologic Complete Response in Patients With Residual Flat Mucosal Lesions After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Case Control Study

2021 ◽  
Author(s):  
Chang-Long Li ◽  
Zhen Guan ◽  
Yi Zhao ◽  
Ting-Ting Sun ◽  
Zhong-Wu Li ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Multivariate Analyses ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Lesion Depth ◽  
Mucosal Lesions

Abstract Background: Accurate prediction of tumor response to neoadjuvant chemoradiotherapy (nCRT) remains challenging. There are few studies on pathologic complete response (ypCR) prediction in patients with residual flat mucosal lesions after treatment. This study aimed to identify variables for predicting the ypCR in patients with residual flat mucosal lesions after nCRT for locally advanced rectal cancer (LARC). Methods: Patients with residual flat mucosal lesions after nCRT who underwent radical resection between 2009 and 2015 were retrospectively collected through the LARC database at Peking University Cancer Hospital. Univariate and multivariate analyses of the association between clinicopathological factors and ypCR were performed, and a nomogram was constructed by incorporating the significant predictors. Results: Out of the 246 patients with residual flat mucosal lesions that were included in the final analysis, 56 (22.8%) had ypCR. Univariate and multivariate analyses showed that posttreatment serum carcinoembryonic antigen (post-nCRT CEA) ≤ 5 ng/ml, magnetic resonance-tumor regression grade (MR-TRG) 1 to 3, and residual mucosal lesion depth = 0 mm were significantly associated with a higher rate of ypCR. A nomogram was developed with a C-index of 0.735, and the calibration curve showed that the nomogram model had good predictive consistency. Conclusion: Post-nCRT CEA ≤ 5 ng/ml, MR-TRG 1 to 3, and residual mucosal lesion depth = 0 mm were predictive factors for ypCR in LARC patients with residual flat mucosal lesions after nCRT. We believe that mucosal re-evaluation before surgery is important as it may contribute to decision-making and facilitating non-operative management or organ preservation.

A randomized phase II study of neoadjuvant chemoradiotherapy with 5-FU/leucovorin or irinotecan/S1 in patients with locally advanced rectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 511-511 ◽  
Author(s):  
Minkyu Jung ◽  
Sang Joon Shin ◽  
Seungtaek Lim ◽  
Ji Soo Park ◽  
Woong Sub Koom ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
P Value ◽  
Preoperative Radiation ◽  
Curative Surgery

511 Background: The purpose of this study was to evaluate rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) with 5-FU/leucovorin (FL) versus Irinotecan/S-1 (IS) and surgery followed by fluoropyrimidine based adjuvant chemotherapy. Methods: Patients with resectable, locally advanced (cT3-4 and/or cN positive) adenocarcinoma of rectum were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25-28 daily fractions) and concomitant chemotherapy with bolus injections of 5-FU 400 mg/m2/day and LV 20 mg/m2/day for 3 consecutive days every 4 weeks for 2 cycles (FL group), or with irinotecan 40 mg/m2 on days 1, 8, 15, 22, 29 and S-1 35mg/m2 twice on the day of irradiation (Monday-Friday) (IS group). Curative surgery was performed for about 4-8 weeks after the completion of chemoradiotherapy. Postoperative chemotherapy regimen is FL. The primary endpoint was pCR rate. Results: 142 eligible patients were randomly assigned. Of 142, 130 patients (91.5%) underwent total mesorectal excision. The pCR was achieved 11 (17.2 %) of 64 patients in the FL group and was 16 (24.2%) of 66 patients in the IS group (p=0.1). When pCR was combined with few residual cells, the rate was significantly higher in IS group compared to FL group (57.6 % vs. 39.1 %, p-value=0.035). Preoperative rate of grade 3-4 toxicity was 1.4% with FL and 7.0 % with IS group (p=0.095). Conclusions: The results have suggested that neoadjuvant CRT using IS is feasible and effective for patients with locally advanced rectal cancer. Longer follow-up is needed to assess survival. Clinical trial information: NCT01269216.

scholarly journals Mutational and Clinical Predictors of Pathologic Complete Response in the Treatment of Locally Advanced Rectal Cancer

2013 ◽  
Vol 45 (1) ◽  
pp. 34-39 ◽  
Author(s):  
Andrea L. Russo ◽  
David P. Ryan ◽  
Darrell R. Borger ◽  
Jennifer Y. Wo ◽  
Jackie Szymonifka ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Predictors
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