scholarly journals A Comparison of Diagnostic Performance of Signal Intensity and Volume Related MRI Multiparameters for Assessing Different Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy

2020 ◽  
Author(s):  
Zhengwu Tan ◽  
Lan Zhang ◽  
Lan Cheng ◽  
Lingling Xie ◽  
Zhenyu Lin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Signal Intensity ◽  
Diagnostic Performance ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Poor Response ◽  
Complete Response ◽  
Change Rate ◽  
Potential Biomarker ◽  
Moderate Response

Abstract Background: “Wait-and-see”, has been proposed as a possible method of treatment in patients with locally advanced rectal cancer (LARC) after chemoradiotherapy (CRT), MR is important to predict the pathological tumor regression grade(TRG) to preoperative CRT. This study aims to evaluate the diagnostic value of signal intensity (SI) and volume (V) change rate in magnetic resonance imaging (MR) and determine which ones perform best as a potential biomarker for predicting pathological TRG to preoperative CRT in patients with LARC.Methods: A retrospective analysis of 82 patients with LARC, for whom clinical and imaging data were retrieved from our institute was conducted between Oct 2017and Oct 2019. Patients underwent pre- and post-CRT T2-weighted (T2W), diffusion-weighted (DW)/apparent diffusion coefficient (ADC) and contrast-enhanced T1-weighted (ceT1W). V, difference of volume between pre-CRT and post-CRT tumor (△V), V of tumor reduction rate (%△V), as well as SI of tumor (SIt), SI of muscle (SIm), relative SI ratio of tumor/muscle (SIR), changed difference SIR between pre- and post-CRT SIR (△SIR), SIR of tumor changed rate (%△SIR) on T2W, ADC and ceT1W were measured. All of LARC after CRT were confirmed pathologically and classifed into histologic TRG: TRG 0 (complete response), TRG 1 (moderate response), TRG 2 (minimal response), TRG 3 (poor response). Descriptive statistics and areas under the receiver operating characteristic curves (ROC) were generated to compare performance of %△V and %△SIR on T2W, DW, ceT1W for distinguishing between different pathological TRG.Result: Of the 82 patients, TRG 0 (16), TRG 1 (15), TRG 2 (35), TRG 3 (16).Except for ADC-%△SIR, the remaining %△V and %△SIR on T1W, ADC/DWI, ceT1W showed statistics significance between four groups. There was not distinguishable between TRG 1 and TRG 2, TRG 2 and TRG 3 by %△V and/ or %△SIR, the remaining different TRG all were identified by %△V and/ or %△SIR on T2W, ADC/DWI, ceT1W. Compared with other individual %△V or %△SIR, the combination of DW-%△V and T2W-%△SIR (DW-%△V * T2W-%△SIR) yielded higher AUCs to predict TRG 0 from TRG 2 (AUCs: 0.954, sensitivity: 93.75%, specificity: 97.14%) and TRG 3 (AUCs: 1.000, sensitivity: 100%, specificity: 100%), although AUC of all had not significant differences between TRG groups. there was statistically significant differences in post-CRT T restage and ypT stage between fours groups, respectively, but the agreement between post-CRT T restage and ypT is low ( kappa=0.191).Conclusions: V and/or SIR change rate on T2W, DW, ceT1W with high diagnostic performance could be useful in differentiating complete response from non-complete response; SIR change rate could be useful for distinguishing between moderate response and poor response.

scholarly journals Comparison of the Diagnostic Performance of Changes in Signal Intensity and Volume From Multiparametric MRI for Assessing Response of Rectal Cancer to Neoadjuvant Chemoradiotherapy

2021 ◽  
Author(s):  
Zhengwu Tan ◽  
Lan Zhang ◽  
Lan Cheng ◽  
Lingling Xie ◽  
Zhenyu Lin Lin ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Signal Intensity ◽  
Diagnostic Performance ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Area Under The Curve ◽  
Advanced Rectal Cancer ◽  
Tumor Regression Grade ◽  
Change Rate

Abstract Background: Tumor regression grade (TRG) correlates with prognosis in patients with locally advanced rectal cancer (LARC), but there is controversy regarding the use of magnetic resonance imaging (MRI) for determining TRG. This study to evaluate the diagnostic value of change rate in signal intensity (SI) and volume (V) from MRI to TRG following preoperative chemoradiotherapy (CRT) in patiens with LARC.Materials and methods: This retrospective analysis examined 82 LARC patients who were admitted to our institution between Oct 2017 and Oct 2019. Patients underwent pre- and post-CRT T2-weighted (T2W), diffusion-weighted (DW)/apparent diffusion coefficient (ADC), and contrast-enhanced T1-weighted (ceT1W) MRI. Change rate of volume and relative SI ratio(%△V and %△SIR) from each sequence were determined. All LARCs were confirmed pathologically and classified into TRG 0, 1, 2 and 3. Descriptive statistics and receiver operating characteristic (ROC) analysis, with calculation of area under the curve (AUC), were used to compare the diagnostic performances. Results: Sixteen patients had TRG-0, 15 had TRG-1, 35 had TRG-2, and 16 had TRG-3. Except for ADC-%△SIR, the remaining%△V and %△SIR on T1W, DWI, and ceT1W had significant differences among the four groups. %△V and/or %△SIR did not distinguish TRG-1 from TRG-2 nor TRG-2 from TRG-3, but differences between other TRGs were identified by %△V and/or %△SIR on T2W, DWI, and ceT1W. The combined use of DW-%△V and T2W-%△SIR provided the best diagnostic performance in distinguishing of TRG-0 from TRG-2 (AUC: 0.954) and from TRG-3 (AUC: 1.000).Conclusions: Preoperative MRI of LARC patients can determine TRG and may improve selection of the preoperative therapy.

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]

Serial ctDNA analysis as a real-time indicator of neoadjuvant chemoradiotherapy in rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3569-3569 ◽  
Author(s):  
Jiaolin Zhou ◽  
Guole Lin ◽  
Yuhua Gong ◽  
Yanyan Zhang ◽  
Yan-Fang Guan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Lymph Node ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Lymph Node Involvement ◽  
Tumor Regression Grade ◽  
Treatment Intensification

3569 Background: Neoadjuvant chemoradiotherapy (nCRT) is nowadays the standard of care for the locally advanced rectal cancer (LARC). However, there is no effective method to predict patients’ possible benefits from nCRT and monitor the response to it. Methods: Patients with locally advanced middle and low rectal cancer of stage cT3-4N0M0 or cTanyN+M0 were enrolled from August 2017 to July 2018. All patients received nCRT with long-term radiation plus fluorouracil based chemotherapy, followed by the radical surgery. Serial plasma samples were collected pre-nCRT, during nCRT, and preoperatively (8 weeks after the completion of nCRT). Somatic mutations were detected with next-generation sequencing using a 1021-gene panel with peripheral blood lymphocyte DNA as a germline control. Results: This prospective cohort study enrolled 61 patients with rectal cancer. The pathological complete response (pCR) rate and the downstage rate was 31% (19/61) and 80% (49/61), respectively. ctDNA was detectable in 77% (47/61), 18% (11/61) and 13% (8/61) of blood samples obtained pre-nCRT, during nCRT and preoperatively, respectively. No significant association was observed between pre-nCRT ctDNA status with any clinicopathological factors, including age, gender, differentiation or tumor circumferential extent. Among the 8 patients with detectable ctDNA preoperatively, pathological tumor regression grade (TRG) of CAP 2-3 were observed and hepatic metastasis was found in 4 patients within 2 months. For patients with undetectable pre-operative ctDNA, a higher proportion archived pathological downstaging (85% vs 50%). The correlation between preoperative ctDNA status and achievement of pathological downstage was independent of age, gender or differentiation (p = 0.02). In addition, preoperative ctDNA positivity was associated with the persistently involved lymph node (p = 0.02). However, neither pre-nCRT nor during-nCRT ctDNA status was associated with pathological downstaging or persistently lymph node involvement. Conclusions: Detectable ctDNA after the completion of nCRT is a predicator of unsatisfactory curative effect of patients with LARC, which might indicate novel treatment intensification studies. Clinical trial information: NCT03042000.

scholarly journals One to Two Cycles of Consolidation Chemotherapy With Capecitabine After Neoadjuvant Chemoradiotherapy Does Not Benefit Low-Risk Patients With Locally Advanced Middle-Low Rectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Xueqing Sheng ◽  
Shuai Li ◽  
Yangzi Zhang ◽  
Jianhao Geng ◽  
Hongzhi Wang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Multivariate Logistic Regression Analysis ◽  
Complete Response ◽  
Low Risk ◽  
Consolidation Chemotherapy ◽  
Chemotherapy Group ◽  
Significant Difference

Background and ObjectiveOrgan preservation can enable locally advanced rectal cancer (LARC) patients with clinical complete response (cCR) after neoadjuvant treatment to maintain quality of life. In this study, we aimed to evaluate whether one or two cycles of capecitabine after neoadjuvant chemoradiotherapy (NCRT) without extending the interval between the end of NCRT and surgery could increase the complete response (CR) rate in low-risk middle-low LARC patients.Material and MethodsWe retrospectively evaluated middle-low LARC patients with low risk defined as clinical T2-3b, mesorectal fascia-clear, and extramural vascular invasion-negative by magnetic resonance imaging (MRI), treated between January 2015 and July 2019. Patients were divided into two groups according to whether consolidation chemotherapy was administered after NCRT. Patients in the consolidation chemotherapy group received one or two cycles of capecitabine (1000 mg/m2 twice daily from days 1 to 14). The main outcome was the CR rate, including pathological CR (pCR) and cCR.ResultsA total of 169 patients, 105 in the consolidation chemotherapy group and 64 in the non-consolidation chemotherapy group, were included in the study, and the median follow-up was 37.2 months (range, 0.4–71.2 months). Seventeen patients achieved cCR and the remaining 152 underwent surgery after neoadjuvant treatment. There was no significant difference in the CR rate (39.0% vs. 35.9%, p=0.686), ypT0-2N0 rate (65.2% vs. 63.3%, p=0.812), or ypN0 rate (83.7% vs. 88.3%, p=0.503) between the consolidation chemotherapy and non-consolidation chemotherapy groups. Among the patients achieved cCR, 3 (17.6%) experienced regrowth in the rectum and 2 (11.8%) experienced distant metastasis. There was also no significant difference in the 3-year disease-free survival (87.4% vs 85.9%, p=0.971) in patients who underwent surgery between the two groups. Multivariate logistic regression analysis indicated that normal Carcinoma Embryonic Antigen (CEA) levels (p = 0.001) were associated with a higher CR rate. Moreover, there were no significant differences in the incidences of grade ≥2 acute toxicities during neoadjuvant treatment.ConclusionAlthough there was no increase in treatment-related toxicities between the two groups, simply adding one or two cycles of capecitabine after NCRT might be insufficient to benefit low-risk middle-low LARC patients.

scholarly journals Factors Predicting Pathological Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer: The Experience of a Single Institution with 269 Patients (STONE-01)

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6074
Author(s):  
Michele Fiore ◽  
Pasquale Trecca ◽  
Luca E. Trodella ◽  
Roberto Coppola ◽  
Marco Caricato ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Female Gender ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Time Interval ◽  
Interval Time ◽  
Time To Surgery

Aims: The aim of this study was to define a potential benefit of pathological complete response rate (pCR) and downstaging rate after neoadjuvant chemoradiotherapy (CRT) in relation to treatment and patient factors in locally advanced rectal cancer. Methods: We performed a retrospective cohort study. Patients were divided according to chemotherapy regimens concurrent to radiotherapy (1-drug vs. 2-drug) and according to the time interval between the end of CRT and surgery (≤8 weeks vs. >8 weeks), as well as in relation to specific relevant clinical factors. Logistic regression was used to estimate the independent factors for pCR and downstaging. Results: 269 patients were eligible for this study. Overall, pCR and downstaging rates were 26% and 75.4%, respectively. Univariate analysis showed that female gender (p = 0.01) and time to surgery >8 weeks (p = 0.04) were associated with pCR; age > 70 years (p = 0.05) and time to surgery >8 weeks (p = 0.002) were correlated to downstaging. At multivariate analysis, interval time to surgery of >8 weeks was the only independent factor for both pCR and downstaging (p = 0.02; OR: 0.5, CI: 0.27–0.93 and p = 0.003; OR: 0.42, CI: 0.24–0.75, respectively). Conclusions: This study indicates that, in our population, an interval time to surgery of >8 weeks is an independent significant factor for pCR and downstaging. Further prospective studies are needed to define the best interval time.

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