Chemoradiotherapy In Rectal Cancer Patients Research Articles

556P Predicting the efficacy of neoadjuvant chemoradiotherapy in rectal cancer patients based on dynamic tumor-informed ctDNA-MRD

556P Predicting the efficacy of neoadjuvant chemoradiotherapy in rectal cancer patients based on dynamic tumor-informed ctDNA-MRD

PO-1394 The role of hypofractionated preoperative chemoradiotherapy in rectal cancer patients

PO-1394 The role of hypofractionated preoperative chemoradiotherapy in rectal cancer patients

A nomogram prediction model for lymph node metastasis risk after neoadjuvant chemoradiotherapy in rectal cancer patients based on SEER database.

Rectal cancer patients who received neoadjuvant chemoradiotherapy (CRT) may have a lower cancer stage and a better prognosis. Some patients may be able to avoid invasive surgery. It is critical to accurately assess lymph node metastases (LNM) after neoadjuvant chemoradiotherapy. The goal of this study is to identify clinical variables associated with LNM and to develop a nomogram for LNM prediction in rectal cancer patients following nCRT. From 2010 to 2015, patients were drawn from the Surveillance, Epidemiology, and End Results (SEER) database. To identify clinical factors associated with LNM, the least absolute shrinkage and selection operator (LASSO) aggression and multivariate logistic regression analyses were used. To predict the likelihood of LNM, a nomogram based on multivariate logistic regression was created using decision curve analyses. The total number of patients included in this study was 6,388. The proportion of patients with pCR was 17.50% (n=1118), and the proportion of patients with primary tumor pCR was 20.84% (n = 1,331). The primary tumor was pCR in 16.00% (n=213) of the patients. Age, clinical T stage, clinical N stage, and histology were found to be significant independent clinical predictors of LNM using LASSO and multivariate logistic regression analysis. The nomogram was developed based on four clinical factors. The 5-year overall survival rate was 78.9 percent for those with ypN- and 66.3 percent for those with ypN+, respectively (P<0.001). Patients over 60 years old, with clinical T1-2, clinical N0, and adenocarcinoma may be more likely to achieve ypN0. The watch-and-wait (WW) strategy may be considered. Patients who had ypN0 or pCR had a better prognosis.

Difference in prognostic impact of lateral pelvic lymph node metastasis between pre- and post-neoadjuvant chemoradiotherapy in rectal cancer patients.

The prognostic significance and treatment of lateral pelvic lymph node metastasis (mLPLN) in rectal cancer patients receiving neoadjuvant chemoradiotherapy (nCRT) are not well understood. In this study, we evaluated the impact of mLPLN identified in imaging modality on outcomes. Between January 2008 and December 2016, 1,535 patients who underwent radical resection following nCRT were identified. The association between mLPLN and disease-free survival (DFS), overall survival (OS), local recurrence-free survival (LRFS), and pelvic recurrence-free survival (PRFS) was analyzed, along with risk factors associated with OS and DFS. Overall, 329 (21.4%) of the 1,535 patients experienced disease recurrence; 71 (4.6%) had local recurrence, 25 (1.6%) had pelvic recurrence, and 312 (20.3%) had distant recurrence. The pre- and post-nCRT mLPLN (-) groups had better DFS, LRFS, PRFS, and OS than the (+) groups. LPLN sampling (LPLNs) was implemented in 24.0% of the pre-nCRT mLPLN (+) group and in 28.8% of the post-nCRT mLPLN (+) group. There was no significant difference in OS and LRFS between LPLNs group and no LPLNs group in pre- and post-nCRT mLPLN (+) groups. Pre-nCRT mLPLN was associated with poor OS (hazard ratio [HR], 1.43; P = 0.009) and post-nCRT mLPLN was associated with poor DFS (HR, 1.49; P = 0.002). Pre- and post-nCRT mLPLN (+) have different prognostic effects. Post-nCRT mLPLN appears to be more important for disease control. However, pre-nCRT mLPLN should not be disregarded when devising a treatment strategy since it is an independent risk factor for OS.

Prognostic significance of lymph node yield on oncologic outcomes according to tumor response after preoperative chemoradiotherapy in rectal cancer patients.

This study aimed to evaluate the predictive value of lymph node yield (LNY) for survival outcomes according to tumor response after preoperative chemoradiotherapy (PCRT) in patients with rectal cancer. This study was a retrospective study conducted in a tertiary center. A total of 1,240 patients with clinical stage II or III rectal cancer who underwent curative resection after PCRT between 2007 and 2016 were included. Patients were categorized into the good response group (tumor regression grade [TRG], 0-1) or poor response group (TRG, 2-3). Propensity score matching was performed for age, sex, and pathologic stage between LNY of ≥12 and LNY of <12 within tumor response group. The primary outcome was 5-year disease-free survival (DFS) and overall survival (OS). LNY and positive lymph nodes were inversely correlated with TRG. In good responders, 5-year DFS and 5-year OS of patients with LNY of <12 were better than those with LNY of ≥12, but there was no statistical significance. In poor responders, the LNY of <12 group had worse survival outcomes than the LNY of ≥12 group, but there was also no statistical significance. LNY of ≥12 was not associated with DFS and OS in multivariate analysis. LNY of <12 showed contrasting outcomes between the good and poor responders in 5-year DFS and OS. LNY of 12 may not imply adequate oncologic surgery or proper staging in rectal cancer patients treated by PCRT. Furthermore, a decrease in LNY should be comprehended differently according to tumor response.

Distal spread and tumor regression patterns following preoperative chemoradiotherapy in rectal cancer patients

This study aimed to evaluate the regression pattern with the distal intramural spread (DIS) of rectum cancer after preoperative chemoradiation. Specimens from 56 patients who underwent radical resection after preoperative chemoradiation for rectal cancer were examined. The regression pattern (total, fragmented) of the tumor was recorded. DIS status was evaluated by creating sections 0.2 to 0.3 cm thick. A single macroscopic residual area was detected in all specimens. In 10 patients (17.8 %), pathologically complete responses were identified, and DIS was detected in 33 patients (58.9%). The average DIS distance was 0.56± 0.3 cm (range 0.2 – 1.8 cm); the spread was < 1 cm in 87.9% of the patients (29/33). The overall survival rates for 5 and 7 years were 76.8% and 73.2%, respectively. The survival rates between patients with and without DIS were not statistically different (94.6± 5.5 vs. 75.1 ± 10.2 months, respectively). In all of the patients, tumor regression pattern was total shrinkage of the tumor. A sufficient distal resection margin for rectal cancer after preoperative chemoradiation is 1 cm in the vast majority of cases. However, DIS may exceed 1 cm in a small proportion of patients.

P-54 Higher muscle mass is associated with better response to concurrent neoadjuvant chemoradiotherapy in rectal cancer patients

Sarcopenia (low muscle mass) is an emerging syndrome associated with poor outcome in cancer patients. We investigated the relationship between skeletal muscle index (SMI), psoas muscle index (PMI), and neoadjuvant rectal score (NAR) in a group of patients with locally advanced rectal adenocarcinoma, treated with neoadjuvant concurrent chemoradiotherapy (nCCRT) with capecitabine and surgery.

A Nomogram Based on a Collagen Feature Support Vector Machine for Predicting the Treatment Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients.

The relationship between collagen features (CFs) in the tumor microenvironment and the treatment response to neoadjuvant chemoradiotherapy (nCRT) is still unknown. This study aimed to develop and validate a perdition model based on the CFs and clinicopathological characteristics to predict the treatment response to nCRT among locally advanced rectal cancer (LARC) patients. In this multicenter, retrospective analysis, 428 patients were included and randomly divided into a training cohort (299 patients) and validation cohort (129 patients) [7:3 ratio]. A total of 11 CFs were extracted from a multiphoton image of pretreatment biopsy, and a support vector machine (SVM) was then used to construct a CFs-SVM classifier. A prediction model was developed and presented with a nomogram using multivariable analysis. Further validation of the nomogram was performed in the validation cohort. The CFs-SVM classifier, which integrated collagen area, straightness, and crosslink density, was significantly associated with treatment response. Predictors contained in the nomogram included the CFs-SVM classifier and clinicopathological characteristics by multivariable analysis. The CFs nomogram demonstrated good discrimination, with area under the receiver operating characteristic curves (AUROCs) of 0.834 in the training cohort and 0.854 in the validation cohort. Decision curve analysis indicated that the CFs nomogram was clinically useful. Moreover, compared with the traditional clinicopathological model, the CFs nomogram showed more powerful discrimination in determining the response to nCRT. The CFs-SVM classifier based on CFs in the tumor microenvironment is associated with treatment response, and the CFs nomogram integrating the CFs-SVM classifier and clinicopathological characteristics is useful for individualized prediction of the treatment response to nCRT among LARC patients.

MCQs on "Factors affecting pathological response and survival following neoadjuvant chemoradiotherapy in rectal cancer patients".

MCQs on "Factors affecting pathological response and survival following neoadjuvant chemoradiotherapy in rectal cancer patients".

Factors affecting pathological response and survival following neoadjuvant chemoradiotherapy in rectal cancer patients.

Despite all advanced treatment methods for rectal cancer, not all patients can provide an adequate response, and hence, possible prognostic factors must be evaluated. The aim of this study was to evaluate the relationship between systemic inflammatory markers and pathological response, overall survival (OS) and disease-free survival (DFS) in patients treated with neoadjuvant chemoradiotherapy (nCRT). We evaluated data of 117 patients for the period 2010 to 2017. Serum measurements of albumin, hemoglobin, C-reactive protein, modified Glasgow prognostic score (mGPS), and white cell counts were obtained. Rodel scoring system was used to determine pathologic tumor regression. Overall, 77% of the patients were in the good response group according to the radiological images. A total of 48% of patients were categorized as a good pathologic response. Pathologic response to treatment was associated with a mGPS of 0 (P = 0.001), normal platelet lymphocyte ratio (PLR) (P = 0.003), TNM stage (P = 0.03), pathologic T stage (P = 0.001), radiologic response to nCRT (P = 0.04), tumor differentiation (P = 0.001), lymphovascular invasion (LVI) (P = 0.001) and perineural invasion (P = 0.02). LVI (P = 0.04), albumin level (P = 0.05), C-reactive protein (P = 0.01), neutrophil platelet score (NPS) (P = <0.001) and mGPS (P = 0.01) had a statistically significant effect on OS. Operation type (P = 0.03), tumor differentiation (P = 0.01), depth of invasion (P = 0.03), NPS (P < 0.01), mGPS (P = 0.01), PLR (P = 0.004), neutrophil-lymphocyte ratio (P = 0.01) and LVI (P = 0.05) were statistically significant on DFS. There was an association between systemic inflammatory markers and pathologic response and also, between OS and DFS. This study can be preliminary data for prospective controlled studies.

Impact of dose-capping chemotherapy in concurrent chemoradiotherapy in rectal cancer patients.

The study evaluated the effect of chemotherapy dose-capping on disease recurrence, toxicity and survival of rectal cancer patients treated with chemoradiotherapy (CRT). 601 consecutive rectal cancer patients treated with concurrent CRT were retrospectively analysed. Dose-capped patients were defined as having a body surface area (BSA) ≥2.0 m2 and who received <95% full weight-based chemotherapy dose. Binary logistic regression was used to study the factors associated with the outcome variables (capped vs. uncapped). Kaplan-Meier estimation evaluated significant predictors of survival. The median follow-up time was 7.54 years. The rate of disease recurrence was significantly higher in dose-capped patients (35%) compared to those without dose-capping (24%, P = 0.016). The adjusted odds ratio for dose-capped patients experiencing recurrence was 1.64 compared to uncapped patients (95% CI, 1.10-2.43). Overall, dose-capped patients were less likely to experience significant toxicity requiring dose reduction and/or treatment break when compared to uncapped patients (15% and 28% respectively, P = 0.008).There was significant differences in PFS between capped and uncapped group (77% vs. 85%; P = 0.017). The 5-year OS in the capped group was 75.0%, and 80% in the uncapped group (P = 0.149). Rectal cancer patients treated with dose-capped CRT were at increased risk of disease recurrence. Patients dosed by actual BSA did experience excessive toxicity compared to dose-capped group. We recommend that chemotherapy dose-capping based on BSA should not be practiced in rectal cancer patients undergoing CRT.

Evaluation of Tissue and Circulating miR-21 as Potential Biomarker of Response to Chemoradiotherapy in Rectal Cancer.

Response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (RC) is quite variable and it is urgent to find predictive biomarkers of response. We investigated miR-21 as tissue and plasma biomarker of response to CRT in a prospective cohort of RC patients; The expression of miR-21 was analyzed in pre- and post-CRT rectal tissue and plasma in 37 patients with RC. Two groups were defined: Pathological responders (TRG 0, 1 and 2) and non-responders (TRG 3). The association between miR-21, clinical and oncological outcomes was assessed; miR-21 was upregulated in tumor tissue and we found increased odds of overexpression in pre-CRT tumor tissue (OR: 1.63; 95% CI: 0.40–6.63, p = 0.498) and pre-CRT plasma (OR: 1.79; 95% CI: 0.45–7.19, p = 0.414) of non-responders. The overall recurrence risk increased with miR-21 overexpression in pre-CRT tumor tissue (HR: 2.175, p = 0.37); Significantly higher miR-21 expression is observed in tumor tissue comparing with non-neoplastic. Increased odds of non-response is reported in patients expressing higher miR-21, although without statistical significance. This is one of the first studies on circulating miR-21 as a potential biomarker of response to CRT in RC patients.

545P - Feasibility of chemoradiotherapy in rectal cancer patients with peritumoral abscesses and fistulas: A case-control non-inferiority trial

BackgroundNeoadjuvant chemoradiotherapy (CRT) is a standard treatment for patients with locally advanced rectal cancer and is effective as a palliative care in patients with nonresectable tumors. Unfortunately CRT is often being withheld for patients with tumor-associated complications due to safety concerns. Literature search reveals only case reports and neither supports nor declines additional risks of CRT in this patient group. The aim of this study was to determine feasibility of CRT in rectal cancer with peritumoral abscesses and fistulas. MethodsPatients with locally advanced or recurrent rectal cancer with peritumoral abscesses and fistulas were included in the study group. The control group consisted of T4 locally advanced or recurrent rectal cancer patients without complications, both groups received long-course neoadjuvant CRT. Groups were matched by age, previous treatment, treatment year. The primary endpoint was CRT toxicity. Secondary endpoints included postoperative morbidity (Clavien-Dindo), pathologic complete response (pCR) and 2year PFS. Results30 patients were included in each group. Patients in the main group had following tumor-associated complications: perianal fistula (n=11), abdominal wall fistula (n=1), rectovaginal fistula (n=9), rectovesical fistula (n=4), peritumoral abscess (n=17). Grade 3-4 toxicity was observed in 2 (6.66%) vs 3 (10%) patients, non-inferiority was confirmed (p=0.0326). Grade 3-4 postoperative complications were observed in 2 (7.14%) patients in the main group and in 3 (10.7%) patients in the control group (p=0.639) with no cases of mortality. pCR was achieved in 2 (7.14%) and 5 (17.8%) patients accordingly (p=0.225). Median follow-up was 25.2 months in the main group and 27.4 months in the control group. Two-year OS was 69% vs 100% (p=0.11), 2-year PFS was 65% vs 78% (p=0.434). ConclusionsPeritumoral abscesses and fistulas should not be considered as contraindication to neoadjuvant chemoradiotherapy. CRT is feasible and safe in patients with tumor-associated complications. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in Rectal Cancer Patients

Standard Dose Versus High Dose of Radiotherapy in Rectal Preservation With Chemo-radiotherapy in Rectal Cancer Patients

Evaluation of Dworak grading system as a prognostic indicator after neoadjuvant chemoradiotherapy in rectal cancer patients.

e15053 Background: The objective of this study was to assess the prognostic role of Tumor Regression Grading (TRG) according to the Dworak system on progression free survival (PFS) after chemoradiotherapy (CRT) in locally advanced rectal cancer. Methods: In total, 159 patients with locally advanced rectal cancer who underwent neoadjuvant CRT from January 2007 and December 2016 were enrolled. PFS (any relapse after surgery) was tested against TRG (Dworak grade 1+2 versus Dworak grade 3+4) and other potential risk factors (age, gender, pre- and postoperative T-stage, pre- and postoperative N-stage, grading, lymph invasion, vessel invasion, chemotherapy regime, resection margin, treatment delay). Risk factors with a highly significant influence (p &lt; 0.01) in the univariate Kaplan-Meier (KM) estimation were tested for independence using the multivariate cox regression model. Results: With a mean follow-up of 42.5 months, 5 years and 10 years estimated PFS for all patients was 60.1% and 49.1% respectively. Estimation of 5 years and 10 years PFS was 49.7% and 45.5% for TRG Dworak grade 1+2 (n = 109) and 83.8% and 67% respectively for TRG Dworak grade 3+4 (n = 50). This difference was highly significant (p &lt; 0.001). Other highly significant risk factors were postoperative N-stage (negative versus positive), lymph invasion (L0 versus L1), and resection margin (R0 versus R1/2). In the multivariate analysis, only TRG and post-op N-stage were identified as independent risk factors for PFS. Conclusions: In this analysis, Dworak Tumor Regression Grading appears to be a prognostic marker for oncologic outcomes in locally advanced rectal carcinoma patients treated with neoadjuvant CRT.

Prognostic Significance of Clinicopathological and Molecular Features After Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients

This study evaluated clinicopathological and molecular features and their prognostic impact on patients with locally advanced rectal cancer (LARC) who received preoperative chemoradiotherapy (CRT). We retrospectively gathered data from 284 patients with LARC who underwent total mesorectal excision (TME) after CRT. In the univariate analysis, lower yield pathologic T (ypT) category, yield pathologic N (ypN) category, yield pathologic TNM (ypTNM) stage, as well as the absence of lymphovascular invasion (LVI) and perineural invasion (PNI), were significantly associated with better disease-free survival (DFS) and overall survival (OS). Meanwhile, the expression of Ki-67, p53, and the mismatch repair (MMR) status showed no association with clinical outcomes. A multivariate survival analysis revealed that ypT category and LVI were independent prognostic factors of a worse DFS (HR=3.081, p-value=0.001; HR=2.818, p-value=0.030) and OS (HR=3.158, p-value=0.006; HR=3.837, p-value=0.014). The ypT category and the presence of LVI were found to be prognostic factors for patients with LARC after CRT followed by TME.

506P - Association between obesity and efficacy of chemoradiotherapy in rectal cancer patients

506P - Association between obesity and efficacy of chemoradiotherapy in rectal cancer patients

Could perfusion heterogeneity at dynamic contrast-enhanced MRI be used to predict rectal cancer sensitivity to chemoradiotherapy?

To evaluate whether perfusion heterogeneity of rectal cancer prior to chemoradiotherapy (CRT) using histogram analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) quantitative parameters can predict response to treatment. Twenty-one patients with histologically proven rectal adenocarcinoma were enrolled prospectively. All patients underwent 1.5T DCE-MRI before CRT. Tumour volumes were drawn on Ktrans and Ve maps, using T2-weighted (W) images as reference, and the following first-order texture parameters of Ve and Ktrans values were extracted: 25th, 50th, 75th percentile, mean, standard deviation, skewness, and kurtosis. After CRT, patients underwent surgery and according with Rödel's tumour regression grade (TRG), they were classified as poor responders "non-GR" (TRG 0-2) and good responders "GR" (TRG 3-4). Differences between GR and non-GR in DCE-MRI first-order texture parameters were evaluated using the Mann-Whitney test, and their role in the prediction of response was investigated using receiver operating characteristic (ROC) curve analysis. Sixteen (76%) patients were classified as GR and five (24%) were non-GR. Skewness and kurtosis of Ve was significantly higher in non-GR (4.886±1.320 and 36.402±24.486, respectively) than in GR patients (1.809±1.280, p=0.003 and 6.268±8.130, p= 0.011). Ve skewness <3.635 was able to predict GR with an area under the ROC curve (AUC) of 0.988, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Ve kurtosis <21.095 was able to predict response with an AUC of 0.963, sensitivity 93.8%, specificity 80%, and accuracy 90.5%. Other parameters were not different between groups or predictors of response. Ve skewness and kurtosis seem to be promising in the prediction of response to CRT in rectal cancer patients.

Abstract 5409: Deep sequencing of circulating microRNAs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy

Abstract Introduction: Rectal cancer accounts for approximately one third of all colorectal cancers (CRC), which belong among leading causes of cancer deaths worldwide. Standard treatment for locally advanced rectal cancer (cT3/4 and/or cN+) includes neoadjuvant chemoradiotherapy (CHRT) with fluoropyrimidines followed by radical surgical resection. MicroRNAs (miRNAs) are small non-coding RNAs playing significant roles in the pathogenesis of many cancers including rectal cancer. MiRNAs could present the new predictive biomarkers of response to CHRT in rectal cancer patients. Materials and Methods: In prospective one-center study, 48 patients diagnosed with rectal cancer who underwent neoadjuvant chemoradiotherapy followed by surgical treatment were included. Blood plasma samples were collected before the neoadjuvant chemoradiotherapy (in 24 cases) and after the therapy at the time of clinical restaging (in 48 cases). Total RNA was isolated from 72 blood plasma samples of 48 patients. cDNA libraries were prepared using CleanTaq Small RNA Library Prep Kit (TriLink BioTechnologies). The final sequencing analyses were performed by Next 500/550 High Output v2 Kit - 75 cycles using the NextSeq 500 instrument (both Illumina). For miRNA mapping and analysis, an online tool Chimira was used. Obtained data were statistically evaluated using the Bioconductor edgeR and DESeq2 package. Results: When miRNA profiles of samples collected before and after therapy were compared, 10 miRNAs showed higher levels and of 2 miRNAs lower levels in pre-treatment specimens (P&amp;lt;0.05). Samples collected at the time of clinical restaging were divided into groups accordingly to tumor regression grade (Dworak score) evaluated after surgical resection of the tumor. Pre-treatment miRNA profiles of patients from CHRT responsive group (Dworak 3+4) and non-responsive group (Dworak 1+2) were compared and 4 miRNAs were upregulated and 4 miRNAs were downregulated in patients with good response to CHRT. Finally, samples collected after the therapy, at the time of clinical restaging, were divided into groups accordingly to the nodal metastatic involvement and 10 miRNAs were identified to be significantly deregulated between groups (P&amp;lt;0.025). Conclusion: Our findings suggest that circulating miRNAs could serve as potential predictive biomarkers of the response to neoadjuvant CHRT in rectal cancer. This work was supported by Ministry of Health of the Czech Republic, grant nr.15-33158A, 15-34553A, 15-31627A, 15-34678A, 16-31314A, 16-31765A and by grant of Czech Grant Agency nr. 16-18257S. Citation Format: Tana Machackova, Dominika Brchnelova, Zdenek Kala, Vladimir Prochazka, Tomas Grolich, Lukas Fiala, Beata Hemmelova, Jaroslav Juracek, Marek Vecera, Jiri Sana, Natalia Gablo, Parwez Ahmad, Marek Svoboda, Ondrej Slaby. Deep sequencing of circulating microRNAs in rectal cancer patients undergoing neoadjuvant chemoradiotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5409.

EP-1491: Neoadjuvant chemoradiotherapy in rectal cancer patients in a 15-year single institutional experience

EP-1491: Neoadjuvant chemoradiotherapy in rectal cancer patients in a 15-year single institutional experience