Chemoradiation Therapy For Rectal Cancer Research Articles

Nonoperative management and local excision after neoadjuvant chemoradiation therapy for rectal cancer.

Locally advanced extraperitoneal rectal cancer represents a significant clinical challenge, and currently, the standard treatment is based on neoadjuvant chemoradiation therapy (CRT) followed by radical surgical resection with total mesorectal excision (TME). In the last 30 years, its management has undergone significant changes due to the improvement of complementary radio- and chemotherapy treatments, the improvement of minimally invasive surgical approaches and the diffusion of organ-sparing approaches, such as nonoperative management, commonly called "watch and wait" (NOM) and local excision (LE), in highly selected patients who achieve a major or complete response to neoadjuvant CRT. This review aimed to critically examine the efficacy and oncological safety of NOM and LE compared to those of standard TME in rectal cancer patients after neoadjuvant CRT. Both the pros and cons of these approaches were strictly analyzed, providing a comprehensive and critical overview of these novel management strategies for rectal cancer.

Transanal endoscopic microsurgery after radiation or chemoradiation therapy for rectal cancer — peculiarities and results

Transanal endoscopic microsurgery after radiation or chemoradiation therapy for rectal cancer — peculiarities and results

Abstract 1017: Impact of microsatellite instability status and immune scores on tumor after neoadjuvant chemoradiation therapy in locally advanced rectal cancer

Abstract Purpose: Neoadjuvant chemoradiation therapy (CRT) is a widely and effectively used preoperative treatment strategy in locally advanced rectal cancers. Tumors demonstrating microsatellite instability (MSI) are known to be infiltrated by higher numbers of lymphocytes and to be characterized by a more favorable prognosis as compared with tumors with intact repair systems, and MSI is the only potential biomarker to predict the outcome of immune checkpoint inhibitors. However, the relationship between MSI and response to neoadjuvant CRT and changes in MSI status after CRT in rectal cancer are not well understood. The aim of the present study was to investigate the MSI status before and after CRT and its association with CRT response in rectal cancer. Materials and methods: Formalin-fixed paraffin-embedded tissue specimens from pre-operative biopsy via sigmoidoscopy and surgical resection of the primary tumor were obtained from 84 rectal adenocarcinoma patients who underwent neoadjuvant CRT between March 2010 and May 2018. MSI assays were performed on DNA extracted from FFPE and matched normal tissues the extracted DNA was amplified by PCR with fluorescent dye-labeled primers targeting five microsatellite loci: BAT25, BAT26, D5S346, D2S123 and D17S250. Three immune biomarker scores were calculated from the 19 patients who were able to perform RNA sequencing analysis to compare the immune activities of the specimens between responder (n = 8) and non-responder (n = 11). The gene lists included in each score calculation were as follows: CXCL9, CXCL10, IDO1, IFNG, HLA-DRA, and STAT1; GZMA and PRF1; and CD247, CD2, CD3E, GZMH, NKG7, PRF1 and GZMK for the interferon-γ (IFN-γ) signature,1 the cytolytic activity2 and the immune signature,3 respectively. Results: Patients were classified, according to Mandard tumor regression grade (TRG), as responders (grade 1 or 2; 25 patients, 29.8%) and non-responders (grade 3, 4 or 5; 59 patients, 70.2%). The TRG of 84 patients was significantly different according to the pre-CRT MSI status (P = 0.024), but was not different according to the post-CRT MSI status among 60 patients who were eligible for the paired MSI test (P = 0.788). Changes in MSI status were observed in 11 of the 60 patients; MSS to MSI-low in 9 patients, MSS to MSI-high in 1 patient, and MSI-low to MSS in 1 patient. All three immune biomarker scores (the IFN-γ signature, the cytolytic activity and the immune signature) were higher in the responder group without significant difference (p = 0.536, p = 0.152, and p = 0.272, respectively). Conclusion: Our findings demonstrated that neoadjuvant CRT modulated the MSI status of rectal cancer and pre-CRT MSI status was significantly associated with response of CRT. Future studies on various immuno-profiles that can influence the CRT response using more samples are needed. Citation Format: Sung Uk Bae, Shin Kim, Sang Jun Byun, Hye Won Lee. Impact of microsatellite instability status and immune scores on tumor after neoadjuvant chemoradiation therapy in locally advanced rectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1017.

Concurrent Aspirin Use Is Associated with Improved Outcome in Rectal Cancer Patients Who Undergo Chemoradiation Therapy.

Simple SummaryThose with a history of colorectal cancer benefit from aspirin following completion of treatment, however, it is believed that this benefit is restricted to patients who have tumors with certain mutations. It is not known whether taking aspirin during active treatment helps patients or whether it depends on tumor genetics in this setting. We investigated 147 patients who underwent chemoradiation for rectal cancer at our institution, including 42 who were taking aspirin at the time of chemoradiation. Concurrent aspirin use was associated with significantly improved tumor control and survival. Genetic analysis of the tumor did not indicate that these benefits were restricted to certain molecular conditions. Interestingly, aspirin was associated with more advantageous immune response in tumor specimens. Based on these findings, the addition of aspirin to chemoradiation should be considered for rectal cancer patients, independent of molecular conditions.Background: The benefit of aspirin in rectal cancer during chemoradiation therapy (CRT) and the factors affecting its efficacy are not well characterized. We compared the outcomes of rectal patients undergoing neoadjuvant CRT based on aspirin use. Methods: Patients undergoing CRT for rectal cancer from 2010 to 2018 were evaluated. Aspirin use was determined by medication list prior to treatment. RNA sequencing and subsequent gene set enrichment analysis was performed on surgically resected specimens. Results: 147 patients underwent neoadjuvant CRT with a median follow-up of 38.2 months. Forty-two patients were taking aspirin prior to CRT. Aspirin users had significantly less local and distant progression, and improved progression-free and overall survival. On RNA-sequencing, neither PI3KCA nor KRAS mutational status were associated with the benefit of aspirin use or tumor downstaging. PTGS2/COX2 expression trended lower in aspirin users, but not with tumor response. Aspirin use was associated with increases of M1 macrophages, plasma cells, CD8+ T cells, and reduction of M2 macrophages in the resected tumor. Conclusions: Concurrent aspirin use during neoadjuvant CRT was associated with improved local and distant tumor control leading to significantly improved survival. Neither mutations in KRAS or PI3CKA, nor the levels of COX-2 expression at the time of resection of the residual tumor were predictive of these aspirin benefits.

MRI Assessment of Complete Response to Preoperative Chemoradiation Therapy for Rectal Cancer: 2020 Guide for Practice from the Korean Society of Abdominal Radiology.

ObjectiveTo provide an evidence-based guide for the MRI interpretation of complete tumor response after neoadjuvant chemoradiation therapy (CRT) for rectal cancer using visual assessment on T2-weighted imaging (T2) and diffusion-weighted imaging (DWI).Materials and MethodsPubMed MEDLINE, EMBASE, and Cochrane Library were searched on November 28, 2019 to identify articles on the following issues: 1) sensitivity and specificity of T2 or DWI for diagnosing pathologic complete response (pCR) and the criteria for MRI diagnosis; 2) MRI alone vs. MRI combined with other test(s) in sensitivity and specificity for pCR; and 3) tests to select patients for the watch-and-wait management. Eligible articles were selected according to meticulous criteria and were synthesized.ResultsOf 1615 article candidates, 55 eligible articles (for all three issues combined) were identified. Combined T2 and DWI performed better than T2 alone, with a meta-analytic summary sensitivity of 0.62 (95% confidence interval [CI], 0.43–0.77; I2 = 80.60) and summary specificity of 0.89 (95% CI, 0.80–0.94; I2 = 92.61) for diagnosing pCR. The criteria for the complete response on T2 in most studies had the commonality of remarkable tumor decrease to the absence of mass-like or nodular intermediate signal, although somewhat varied, as follows: (near) normalization of the wall; regular, thin, hypointense scar in the luminal side with (near) normal-appearance or homogeneous intermediate signal in the underlying wall; and hypointense thickening of the wall. The criteria on DWI were the absence of a hyperintense signal at high b-value (≥ 800 sec/mm2) in most studies. The specific algorithm to combine T2 and DWI was obscure in half of the studies. MRI combined with endoscopy was the most utilized means to select patients for the watch-and-wait management despite a lack of strong evidence to guide and support a multi-test approach.ConclusionThis systematic review and meta-analysis provide an evidence-based practical guide for MRI assessment of complete tumor response after CRT for rectal cancer.

Effect and Safety of Radiation Therapy Boost to Extramesorectal Lymph Nodes in Rectal Cancer

PurposeIn rectal cancer, the presence of extramesorectal/lateral pelvic lymph node (LPN) is associated with higher risk of locoregional and distant recurrences. LPNs are not typically resected during a standard total mesorectal excision (TME) procedure, and the optimal management for these patients is controversial. We assessed the safety and efficacy of adding a radiation therapy boost to clinically positive LPN during neoadjuvant chemoradiation therapy for rectal cancer. Methods and MaterialsWe analyzed nonmetastatic, lymph node positive rectal adenocarcinoma patients treated with neoadjuvant chemoradiation therapy followed by TME between May 2011 and February 2018. Patients without LPN involvement received external beam radiation therapy (45 Gy in 25 fractions) to the primary tumor and regional draining lymph node basins followed by a boost (5.4 Gy in 3 fractions) to gross disease. Patients with clinically positive LPN that would not be removed during TME received an additional boost (up to a total dose between 54.0 and 59.4 Gy) to the involved LPNs. We compared locoregional control, overall survival, progression-free survival, and treatment-related toxicity between these 2 groups. ResultsFifty-three patients were included in this analysis with median follow-up of 30.6 months for the LPN– group (n = 41) and 19.9 months for the LPN+ group (n = 12). There was no difference in 3-year overall survival (90.04% vs 83.33%, P = .890) and progression-free survival (80.12% vs 80.21%, P = .529) between the 2 groups. We did not observe any LPN recurrences. There were no differences in rates of acute grade 3+ or chronic toxicities. ConclusionsDespite the well-documented negative prognostic effect of LPN metastasis, we observed promising outcomes for LPN+ patients treated with an additional radiation boost. Our results suggest that radiation therapy boost to clinically involved, unresected LPN is an effective treatment approach with limited toxicity. Additional studies are needed to optimize treatment strategies for this unique patient subset.

2019 Canadian Surgery Forum Abstracts.

# 01. The future of general surgery training: a Canadian resident nationwide Delphi consensus statement {#article-title-2} Various pedagogical models have been introduced in an attempt to improve and restructure surgical training, but significant obstacles remain. Before implementing national

The Krüppel-like factor (KLF5) as a predictive biomarker in preoperative chemoradiation therapy for rectal cancer.

PurposePreoperative chemoradiation therapy (CRT) has become the standard treatment for patients with locally advanced rectal cancer, 15%–30% of patients still progress while being treated with CRT. The aim of this study was to identify as important biomarker of poor response and evaluate the mechanism associated with CRT resistance.MethodsThis study included 60 human colon tumour pre-irradiation specimens. Expressions of epidermal growth factor receptor (EGFR), p53, Krüppel-like factor 5 (KLF5), C-ern, Ki67 were assessed and correlated with tumor regression grades and complete remission. We added in vitro study with biomarker which has been identified as important biomarker of poor response to evaluate the mechanism associated with CRT resistance.ResultsPathologic complete remission (pCR) was achieved by 9 patients (18%). EGFR and KLF5 were significantly associated with pCR (P = 0.048, P = 0.023, respectfully). And multivariate analysis showed high KLF5 intensity was worse factor for pCR (P = 0.012). In vitro study, radiation or chemotherapy therapy stabilized KLF5 protein levels in a time- and dose-depended manner in HCT116 and Caco-2 cells. KLF5 overexpression in HCT116 stable cell line showed significantly better cell viability by increasing cyclinD1 and b-catenin compared to control cells in MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, suggesting that KLF5 mediates cell survival.ConclusionKLF5 was significantly associated with the presence of KRAS mutations, and KLF5 was an independent poor response predictor of CRT in rectal cancer. Our study is pilot study and more research will be needed in the future.

Genomic Analysis to Predict Response to Neoadjuvant Chemoradiation Therapy in Rectal Cancer

The role of preoperative chemoradiation therapy is well established in the treatment of locally advanced rectal cancer. However, there remains significant heterogeneity in response to CRT, with only 50% of patients having some degree of response to neoadjuvant therapy. Currently, there is no established method to identify the subset of patients that do not response to treatment. Therefore, the purpose of this study was to utilize next generation DNA sequencing to assess for variants among a panel of 160 cancer-related genes to identify gene signatures among patients with pathologic complete response (pCR) compared to patients with no response (NR). A cohort of patients treated with neoadjuvant CRT followed by definitive surgery were selected from our clinical database and pathology archive (N=16). The pCR group included patients who had no evidence of residual tumor on pathologic assessment (N=8). In contrast, the NR group included patients who had >50% original tumor on final assessment. Tumor DNA was extracted from formalin-fixed paraffin-embedded tissue and libraries constructed with Comprehensive Cancer Panel (Qiagen). Sequencing was performed with Illumina NextSeq 500 and alignment was achieved using Biomedical Genomics Workbench with subsequent analysis with Ingenuity Variant Analysis. A comparison of the pretreatment biopsies from non-responders (n=8) versus complete responders (n=8) identified 178 individual variants in 71 genes. However, of these only 2 variants were found in more than one non-responder which were absent in all the complete responders. These variants were found in KDM6A and DNMT3A. Pathway analysis of all the variants found in non-responders identified “colorectal cancer metastasis signaling” as being highly altered. Analysis at the gene level identified 27 variants in 11 genes that were altered in the non-responder compared to the responders. There genes were CTNNB1, PIK3CA, APC, ECT2L, MET, ABL1, ATM, KRAS, AKT1, TP53 and EP300. Several of these genes were represented in the “epithelial-mesenchymal transition pathway”. This preliminary study has identified mutated genes which are present in the pretreatment biopsies of rectal cancer patients who do not respond to neoadjuvant chemoradiation. Genes involved in DNA repair, cell survival and epithelial-mesenchymal transition were amongst the genes altered. Several drug targets including PIK3CA, MET and DNA damage response may offer new avenues for combination therapy for these patients.

Pelvic MRI after induction chemotherapy and before long-course chemoradiation therapy for rectal cancer: What are the imaging findings?

To determine the appearance of rectal cancer on MRI after oxaliplatin-based chemotherapy (ICT) and make a preliminary assessment of MRI's value in predicting response to total neoadjuvant treatment (TNT). In this IRB-approved, HIPAA-compliant, retrospective study between 1 January 2010-20 October 2014, pre- and post-ICT tumour T2 volume, relative T2 signal intensity (rT2SI), node size, signal intensity and border characteristics were assessed in 63 patients (65 tumours) by three readers. The strength of association between the reference standard of histopathological percent tumour response and tumour volume change, rT2SI and lymph node characteristics was assessed with Spearman's correlation coefficient and Wilcoxon's rank sum test. Cox regression was used to assess association between DFS and radiological measures. Change in T2 volume was not associated with TNT response. Change in rT2SI showed correlation with TNT response for one reader only using selective regions of interest (ROIs) and borderline correlation with response using total volume ROI. There was a significant negative correlation between baseline and post-ICT node size and TNT response (r = -0.25, p = 0.05; r = -0.35, p = 0.005, readers 1 and 2, respectively). Both baseline and post-induction median node sizes were significantly smaller in complete responders (p = 0.03, 0.001; readers 1 and 2, respectively). Change in largest baseline node size and decrease in post-ICT node signal heterogeneity were associated with 100% tumour response (p = 0.04). Nodal sizes at baseline and post-ICT MRI correlated with DFS. In patients undergoing post-ICT MRI, tumour volume did not correlate with TNT response, but decreased lymph node sizes were significantly associated with complete response to TNT as well as DFS. Relative T2SI showed borderline correlation with TNT response. • MRI-based tumour volume after induction chemotherapy and before chemoradiotherapy did not correlate with overall tumour response at the end of all treatment. • Lymph node size after induction chemotherapy and before chemoradiotherapy was strongly associated with complete pathological response after all treatment. • Lymph node sizes at baseline and post-induction chemotherapy MRI correlated with disease-free survival.

Neoadjuvant chemoradiation therapy for rectal cancer: current status and perspectives for the surgeon

Modern management of rectal cancer has become increasingly complex over the last decades. The introduction of neoadjuvant chemoradiation to the treatment strategy of locally advanced and distal rectal cancers has added numerous variables that may ultimately affect final surgical or even non-surgical management. Specific chemoradiation regimens, intervals after neoadjuvant treatment completion and tools for the assessment of tumor response may all affect final surgical decision and should be interpreted with care. The present study attempts to provide a review of commonly used neoadjuvant chemoradiation regimens, specific intervals and final surgical or non-surgical management of rectal cancer in current clinical practice.

Neoadjuvant chemoradiation therapy for rectal cancer: current status and perspectives for the surgeon

Neoadjuvant chemoradiation therapy for rectal cancer: current status and perspectives for the surgeon

The value of diffusion kurtosis imaging in assessing pathological complete response to neoadjuvant chemoradiation therapy in rectal cancer: a comparison with conventional diffusion-weighted imaging.

ObjectivesThe aim of this study is to comprehensively evaluate the advantage of diffusion kurtosis imaging (DKI) in distinguishing pathological complete response (pCR) from non-pCR patients with locally advanced rectal cancer (LARC) after neoadjuvant chemoradiation therapy (CRT) in comparison to conventional diffusion-weighted imaging (DWI).Material and MethodsFifty-six consecutive patients diagnosed with LARC were prospectively enrolled and underwent pre- and post-CRT MRI on a 3.0 T MRI scanner. Apparent diffusion coefficient (ADC), mean diffusion (MD) and mean kurtosis (MK) values of the tumor were measured in pre- and post-CRT phases and then compared to histopathologic findings after total mesorectal excision (TME). Both Mann-Whitney U-test and Kruskal-Wallis test were used as statistical methods. Diagnostic performance was determined using receiver operating characteristic (ROC) curve analysis.ResultsFor a total of 56 rectal lesions (pCR, n = 14; non-pCR, n = 42), the MKpre and MKpost values were much lower for the pCR patients (mean±SD, 0.72±0.09 and 0.56±0.06, respectively) than those for the non-pCR patients (0.89±0.11 and 0.68±0.08, respectively) (p < 0.001). The ADCpost and the change ratio of apparent diffusion coefficient (ADCratio) values was significantly higher for the pCR patients (mean±SD, 1.31±0.13 and 0.64±0.34, respectively) than for the non-pCR patients (1.12±0.16 and 0.33±0.27, respectively) (p < 0.001 and p = 0.001, respectively). In addition, the MDpost and the change ratio of mean diffusion (MDratio) (2.45±0.33 vs. 1.95±0.30, p < 0.001; 0.80±0.43 vs. 0.35±0.32, p < 0.001, respectively) also increased, whereas the ADCpre, MDpre and the change ratio of mean kurtosis (MKratio) of the pCR (0.82±0.11, 1.40±0.21, and 0.23±0.010, respectively) exhibited a neglectable difference with that of the non-pCR (p = 0.332, 0.269, and 0.678, respectively). The MKpost showed relatively high sensitivity (92.9%) and high specificity (83.3%) in comparison to other image indices. The area under the receiver operating characteristic curve (AUROC) that is available for the assessment of pCR using MKpost (0.908, cutoff value = 0.6196) were larger than other parameters and the overall accuracy of MKpost (85.7%) was the highest.ConclusionsBoth DKI and conventional DWI hold great potential in predicting treatment response to neoadjuvant chemoradiation therapy in rectal cancer. The DKI parameters, especially MKpost, showed a higher specificity than conventional DWI in assessing pCR and non-pCR in patients with LARC, but the pre-CRT ADC and MD are unreliable.

Predictive value of PET/CT for pathological complete response and survival in patients with locally advanced rectal cancer.

697 Background: A major challenge in identifying candidates for nonoperative management of locally advanced rectal cancer is predicting pathological complete response (pCR) following chemoradiation therapy (CRT). We evaluated the ability of pre- and post-CRT PET imaging to predict pCR and long-term prognosis. Methods: We retrospectively identified patients at our institution from 2002–2015 with locally advanced rectal cancer who underwent CRT, pre- and post-CRT PET imaging, and surgical resection. Logistic regression and Kaplan-Meier estimates were used to analyze the association of PET variables with tumor pCR and survival outcomes. Receiver operator characteristic curves were generated to define optimal cutoff points for predictive PET variables. Results: 140 patients matched the inclusion criteria. The pCR rate was 28%, and median follow-up time was 48 months. On multivariable analysis, pCR was associated with lower median post-CRT SUVmax(3.2 vs 5.2, p=0.009) and higher median SUV percent decrease (72 vs 58%, p=0.009). ROC curves were generated for SUV percent decrease (AUC=0.70) and post-CRT SUV (AUC=0.69) to estimate cutoff points for maximum specificity and sensitivity to predict pCR. Post-CRT SUV &lt;4.3 and SUV percent decrease of &gt;66% were equally predictive of pCR with a sensitivity of 65%, specificity of 72%, PPV of 44%, and NPV of 86%. Median 5-year OS and RFS were significantly improved for patients with post-CRT SUV &lt;4.3 (OS, 86 vs 66%, p=0.01; RFS, 75 vs 52%, p=0.01) or SUV percent decrease of &gt;66% (OS, 82 vs 66%, p=0.05; RFS, 75 vs 54%, p=0.01). Patients with stage III disease and a post-CRT SUV &lt;4.3 were in effect downstaged, with a median 5-year OS equivalent to that of patients with stage II disease (Table 1; 86 vs 86%). Conclusions: PET/CT may be a useful modality in predicting pCR and overall survival in patients undergoing CRT for rectal cancer. Inclusion of pre-CRT PET does not appear to add prognostic value for pCR compared with post-CRT PET alone. Patients with a post-CRT SUV of &gt;4.3 should not be considered for nonoperative management, as an estimated 86% of these patients will not have a pCR.

Role of thymidylate synthase as a predictor of neoadjuvant chemoradiation therapy in rectal cancer

Aim. To study the level of thymidylate synthase gene expression in biopsy material from patients with rectal cancer treated with neoadjuvant chemoradiation therapy. &#x0D; Methods. Analysis of treatment of 101 patients with locally advanced rectal cancer (T3-4, N0-2, M0) was conducted. Measurement of the level of thymidylate synthase gene expression was performed by polymerase chain reaction. To extract ribonucleic acid Qiagen (RNA easy FFPEkit; Qiagen,GmbH,Germany) reagents were used. &#x0D; Results. Cancer pathomorphosis stage TRG 1 was revealed in 23 (22.7%) patients, TRG 2 - in 31 (30.7%) patients, TRG 3 - in 32 (31.7%) patients, complete clinical response (i.e. complete tumor resorption TRG 4) - in 15 (14.9%) patients. Analysis of thymidylate synthase gene expression in patients with poor response to chemoradiation therapy showed that in 34.8% of cases high expression was revealed, while in 65.2% of cases - low expression. Among patients with complete clinical response significant prevalence of patients with high expression of thymidylate synthase gene was revealed - 73.3%, and in 26.7% of patients with pathomorphosis of grade 4 low expression of this gene was registered. In patients with tumor regression grade 2 and 3 no significant difference in patients’ ratio was revealed. The most prominent correlation according to the level of thymidylate synthase gene expression was found in patients without the response to conducted chemoradiation therapy (with prevalence of patients with low expression) and complete tumor regression (with prevalence of patients with high expression). &#x0D; Conclusion. There is inverse correlation between the grade of tumor regression and thymidylate synthase gene expression; evaluation of the level of thymidylate synthase gene expression and response of rectal cancer to neoadjuvant chemoradiation therapy requires further investigation both on molecular and clinical levels.

518P - Circulating tumor cells: a promising marker in predicting tumor response after preoperative chemo-radiation therapy for rectal cancer

518P - Circulating tumor cells: a promising marker in predicting tumor response after preoperative chemo-radiation therapy for rectal cancer

1554P - The role of Krüppel-like factor (KLF5) and its mechanism for treatment resistance in preoperative chemoradiation therapy for rectal cancer

1554P - The role of Krüppel-like factor (KLF5) and its mechanism for treatment resistance in preoperative chemoradiation therapy for rectal cancer

Clinical Significance of the Endoscopic Finding in Predicting Complete Tumor Response to Preoperative Chemoradiation Therapy in Rectal Cancer.

There are reports that suggest conservative treatment when a tumor shows clinically complete response (CR) after preoperative chemoradiotherapy in rectal cancer. The aim of this study is to investigate the association between endoscopic complete response (E-CR) and pathologic CR (pCR) and to determine the sensitivity and specificity of E-CR and its clinical utility after preoperative chemoradiotherapy in rectal cancer. We analyzed prospectively collected data of patients with middle and lower rectal cancers who underwent preoperative chemoradiotherapy, between January 2010 and January 2015. Nineteen patients (17.9%) showed E-CR, and 87 patients showed E-non CR. Twenty-three patients (21.7%) were confirmed to have pCR. E-CR was closely associated with pCR (p<0.001). E-CR reflected pCR with an accuracy of 88.7%, sensitivity of 65.2%, specificity of 95.2%, PPV of 78.9%, NPV of 90.8%, and a p value of <0.001. E-CR after preoperative chemoradiotherapy in rectal cancer is significantly associated with pCR. However, a wait and see policy should be performed carefully with current endoscopic prediction for pCR to avoid inadequate treatment in patients who show E-CR after preoperative chemoradiotherapy.

Correlation between platelet/lymphocyte ratio, neutrophil/lymphocyte ratio and response to neoadjuvant chemoradiation therapy in rectal cancer.

e15140Background: Locally advanced rectal cancer is treated with neoadjuvant chemoradiation, but biomarkers are lacking to predict response to this therapy. Neutrophil/lymphocyte ratio (NLR) and pl...

Factors associated with acute toxicity during chemoradiation therapy for rectal cancer.

734 Background: Acute toxicity may be a factor interfering with receipt of chemoradiation (CRT) therapy for rectal cancer. The purpose of this study was to identify clinical and treatment factors associated with increased acute toxicity in patients receiving CRT therapy for rectal cancer. Methods: We identified patients with rectal adenocarcinoma treated with CRT between 2006-2014 at an NCI-designated cancer center. Patients with metastatic disease or missing treatment information were excluded. Acute toxicity information including weight loss, pain, fatigue, constipation, diarrhea, anorexia, and performance status was extracted from weekly on treatment visit notes. Multivariable logistic regression was used to assess predictors of grade 3+ toxicity using covariates significant on univariable analysis. Results: A total of 148 patients were included with a median age of 59 (range 29-99). The majority of patients were male (55%) and received 5-FU based chemotherapy (82%). During CRT, 35 (24%) patients experienced at least one grade 3+ toxicity: 13 (9%) patients experienced grade 3+ fatigue, 1 (1%) experienced grade 3+ constipation, 11 (7%) experienced grade 3+ diarrhea, 14 (10%) experienced grade 3+ pain, and 11 (7%) experienced grade 3+ anorexia. Eight (5.4%) patients had an ECOG performance status &gt; 3 and 28 (19%) patients had weight loss &gt; 5 lbs during CRT. On multivariable analysis, increased distance from the anal verge (OR 0.78 95% CI 0.636-0.998) was associated with a decreased risk for grade 3+ pain and age &gt; 75 was associated with an increased risk of grade 3+ anorexia (OR 6.07 95% CI 1.067-34.56). Clinical T4 disease was associated with an increased risk of weight loss &gt; 5 lbs (OR 0.17 95% CI 0.100-0.446). On multivariable analysis, there were no factors associated with grade 3+ fatigue, diarrhea, or constipation. There were no factors associated with a decline in performance status to &gt; 3 while on treatment. Conclusions: Our results suggest that rectal cancer patients who are older, have more advanced disease, or with low lying tumors may be at an increased risk for treatment-related toxicity. Identifying predictors of toxicity may allow for tailored interventions to minimize toxicity for these patients.