Association of perineural invasion with outcomes after neodjuvant chemoradiation for locally advanced rectal adenocarcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 750-750
Author(s):  
Priyanka Vinod Chablani ◽  
Phuong Nguyen ◽  
Charles Andrew Robinson ◽  
Xueliang Jeff Pan ◽  
Steve Andrew Walston ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Perineural Invasion ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Rectal Adenocarcinoma ◽  
Residual Tumor ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Resected Specimen ◽  
Free Survival

750 Background: Perineural invasion (PNI) as a prognostic indicator has not been well studied in patients with rectal adenocarcinoma treated with neoadjuvant chemoradiation (nCRT). In this study, we investigated the incidence and prognostic significance of PNI in patients with stages II-III locally advanced rectal cancer treated with nCRT. Methods: We performed a retrospective study of 110 consecutive patients treated with nCRT for locally advanced rectal adenocarcinoma at a single institution from 2004 to 2011. 88 of these patients had residual tumor in the resected specimen after nCRT. We evaluated the association of PNI with clinical outcomes, including disease-free survival (DFS), distant-metastasis-free survival (DMFS), and overall survival (OS), using log-rank and Cox proportional hazard modeling. Results: Of the 88 patients with residual tumor at surgery, 14 patients (16%) had PNI and 74 patients (84%) did not. Baseline distribution of selected variables in the PNI+ and PNI- groups are shown in Table 1. Median follow-up was 27 months (range 0.9 to 84 months). The median DFS was 13.5 months for PNI+ patients and 39.8 months for PNI- patients (p<0.0001). The median DMFS was 13.5 months for PNI+ patients and median not reached (> 40 months) for PNI- patients (p<0.0001). We did not detect a significant association between the presence of PNI and worse OS, perhaps due to a high rate of censored patients in the OS analysis. In a multivariate model including pT stage, pN stage, tumor location, tumor size, type of surgery, and radial margin status, PNI remained a significant predictor of DFS (HR 16.8, 95% CI, 3.7–75.5, p<0.0002) and DMFS (HR 18.9, 95% CI, 4.4–81.9, p<0.0001). Conclusions: For patients with locally advanced rectal cancer treated with nCRT prior to surgical resection, PNI found at the time of surgery is significantly associated with worse DFS and DMFS. [Table: see text]

Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4008-4008 ◽  
Author(s):  
Julio Garcia-Aguilar ◽  
Sujata Patil ◽  
Jin K. Kim ◽  
Jonathan B. Yuval ◽  
Hannah Thompson ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Organ Preservation ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Rank Test ◽  
Type I ◽  
Free Survival

4008 Background: Organ preservation (OP) with a watch and wait strategy (WW) and total neoadjuvant therapy (TNT) are new treatment paradigms for patients with locally advanced rectal cancer. The safety and efficacy of WW and of TNT have not been studied prospectively. Methods: Patients with MRI stage II and III rectal adenocarcinoma were randomized to 4 months of FOLFOX or CAPEOX before (Induction) or after (Consolidation) fluorouracil or capecitabine based chemoradiotherapy (CRT). Patients were re-staged 8-12 weeks after finishing TNT with digital rectal exam, flexible sigmoidoscopy and MRI. Patients with complete or near-complete clinical response were offered WW. Those with incomplete response had total mesorectal excision. The trial was designed so that each arm served as its own single-stage study that discriminates between 3-year disease-free survival (DFS) rates of 75% (historical null) and 85%, with 86% power, and a two-sided type I error of 5%. Secondary objectives included comparing DFS, OP, and distant metastasis-free survival (DMFS) rates between the two arms using the log-rank test. Results: Of 324 patients enrolled, 307 (152 I, 155 C) are currently evaluable for the time-to-event analysis as of 2/1/2020. Median follow-up is 2.1 years; 52 DFS events were observed. Patient demographics and tumor characteristics were generally balanced across the two arms. Full compliance with systemic chemotherapy was 82% and 81% for the I- and C-arms, respectively. The median radiation dose was 5400 cGy for both arms. Table shows 3-y DFS, DMFS, and OP rates. Conclusions: A WW strategy for patients with locally advanced rectal cancer that achieve a clinical complete response to TNT results in organ preservation for a high proportion of patients without compromising survival. Up-front CRT followed by consolidation chemotherapy resulted in a numerically higher WW rate compared to induction chemotherapy followed by CRT. Clinical trial information: NCT02008656 . [Table: see text]

The impact of tumor regression grade on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy

2020 ◽  
Vol 26 (7) ◽  
pp. 1611-1620
Author(s):  
Abdullah Sakin ◽  
Suleyman Sahin ◽  
Nilay Sengul Samanci ◽  
Nurgul Yasar ◽  
Cumhur Demir ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Residual Tumor ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Relapse Free Survival ◽  
Free Survival

Purpose The aim of this study is to investigate the prognostic effect of tumor regression grade (TRG) on long-term survival in locally advanced rectal cancer treated with preoperative chemoradiotherapy. Methods Medical records of 182 patients with locally advanced rectal cancer, who were treated with preoperative chemoradiotherapy followed by surgery between 2002 and 2016, were retrospectively reviewed. TRG was classified into five categories based on the pathological response as follows – TRG1: no viable cancer cell, TRG2: single cancer cell or small groups of cancer cells, TRG3: residual tumor outgrown by fibrosis, TRG4: residual tumor outgrowing fibrosis, TRG5: diffuse residual tumor without regression. TRG1, (TRG2+TRG3), and (TRG4+TRG5) were grouped as complete response, intermediate response, and no response, respectively. Results Of the 182 patients with locally advanced rectal cancer, 112 (61.5%) were male. The mean age was 54.4 (range, 25–87) years. The total number of patients in complete response, intermediate response, and no response group was 24 (13.2%), 105 (57.7%), and 53 (29.1%), respectively. The corresponding five-year relapse-free survival and overall survival rates were 79.8%–92.3%, 74.7%–79.4%, and 55.7%–55.8%, respectively (p < 0.05 for relapse-free survival, p < 0.05 for overall survival). According to ypTNM stage, there was no significant difference in relapse-free survival among TRG groups in ypStage I and II patients (p > 0.05). In ypStage III patients, relapse-free survival was 62 months in no response group vs. not reached in intermediate response group (p < 0.05). According to the ypTNM, there was no significant difference in overall survival among TRG groups in ypStage I, II, and III patients (p > 0.05). In the multivariate analysis, pathological complete response was found to be an independent variable for relapse-free survival and overall survival (hazard ratio (95% confidence interval), 0.34 (0.17–6.77), 0.39 (0.18–0.83), respectively). Conclusion This study showed that patients with pathological complete response to preoperative chemoradiotherapy had longer relapse-free survival and overall survival rates than those with residual disease.

A multicenter phase Ib/II study of DNA-PK inhibitor peposertib (M3814) in combination with capecitabine and radiotherapy in patients with locally advanced rectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS144-TPS144
Author(s):  
Paul Bernard Romesser ◽  
Emma B. Holliday ◽  
Tony Philip ◽  
Rocio Garcia-Carbonero ◽  
Jaume Capdevila ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib

TPS144 Background: Perioperative radiotherapy and chemotherapy, followed by total mesorectal excision, is the standard of care for patients with locally advanced rectal cancer (LARC). However, 1/3 of these patients still develop distant metastases, indicating the need for more effective therapies. In addition, strategies that increase pathological complete response rates are needed to enable non-surgical management of LARC. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway for double-strand break repair. Peposertib (M3814), a potent, selective, orally administered DNA-PK inhibitor, has been shown to potentiate the effect of ionizing radiation in a human colon cancer xenograft model and several colon cancer cell lines. Peposertib is being investigated in several different trials across multiple indications. This Phase Ib/II study (NCT03770689) aims to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of the neoadjuvant treatment combination of peposertib, capecitabine, and radiotherapy (RT) in patients with LARC. Methods: Patients aged ≥18 years with histologically confirmed and resectable Stage II/III rectal adenocarcinoma are eligible. Induction chemotherapy is permitted, but residual disease must first be documented by MRI, digital rectal examination and endoscopy. Patients who received other anticancer therapies or those with prior pelvic RT are excluded. At open-label Phase Ib (open), 18–30 patients (n = 3 per cohort) will receive peposertib + capecitabine (orally, 825 mg/m2 twice daily [BID]) + RT (45–50.4 Gy), 5 days/week. Peposertib 50 mg once daily (QD) was the starting dose. Additional dose levels will range between 100─800 mg QD. Dose escalation is determined by the safety monitoring committee and guided by a Bayesian 2-parameter logistic regression model. At Phase II (planned), 150 patients will be randomized (1:1) to receive oral capecitabine (825 mg/m2 BID) + RT (45–50 Gy), with either oral peposertib (recommended phase II dose [RP2D] or placebo, QD for 5 days/week. Primary objectives are to define a maximum tolerated dose and RP2D (Phase Ib), and to evaluate the efficacy of peposertib + capecitabine + RT in terms of pathological/clinical complete response (Phase II). Secondary objectives include assessment of antitumor activity (Phase Ib), quality of life outcomes (Phase II), and PK of peposertib, and the safety and tolerability of the combination therapy (both phases). To date, one patient has received peposertib 50 mg QD, six patients peposertib 100 mg QD, three patients peposertib 150 mg QD, and three patients peposertib 250 mg QD. Clinical trial information: NCT03770689.

Intensification of neoadjuvant therapy in patients with locally advanced rectal cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 19-28
Author(s):  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
D. V. Kuzmichev ◽  
S. I. Tkachev ◽  
A. A. Aniskin
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

Prognostic Value of Pretreatment Serum CA199 in Patients with Locally Advanced Rectal Cancer Treated with CRT Followed by TME with Normal Pretreatment Carcinoembryonic Antigen Levels

2020 ◽  
pp. 1-6
Author(s):  
Daxin Huang ◽  
Qingliang Lin ◽  
Jianyuan Song ◽  
Benhua Xu
Keyword(s):  
Rectal Cancer ◽  
Carcinoembryonic Antigen ◽  
Prognostic Value ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Carbohydrate Antigen ◽  
Curative Surgery ◽  
Pretreatment Serum

<b><i>Background:</i></b> Elevated pretreatment carcinoembryonic antigen (CEA) levels are related to poor prognosis in patients with locally advanced rectal cancer (LARC) treated with neo-CRT followed by TME. In patients with normal pretreatment CEA levels, the prognostic significance of carbohydrate antigen 199 (CA199) is controversial. <b><i>Objectives:</i></b> The aim of this study was to explore the prognostic value of pretreatment serum CA199 in patients with LARC who had normal pretreatment CEA levels treated with neo-CRT followed by curative surgery. <b><i>Methods:</i></b> A retrospective study of 456 patients with LARC treated with neo-CRT followed by TME between January 2006 and May 2017 was performed. We employed the maximal χ<sup>2</sup> method to determine the CA199 threshold of 9.1 U/mL based on the difference in survival and divided patients into 2 groups. Group 1: patients with pretreatment s-CEA &#x3c; 5 ng/mL and CA199 ≥ 9.1 U/mL. Group 2: patients with pretreatment s-CEA &#x3c; 5 ng/mL and CA199 &#x3c; 9.1 U/mL. Overall survival (OS) across CA199 was assessed using Cox proportional hazard regression models (PS:CEA ≥ 5 ng/mL was seen as elevated). <b><i>Results:</i></b> Multivariate analyses demonstrated that the following factors were significantly related to OS in patients with LARC with normal pretreatment CEA levels: ypT (odds ratio [OR] 1.863, <i>p</i> = 0.030), ypN (OR 1.622, <i>p</i> = 0.026), and pretreatment CA199 levels (OR 1.886, <i>p</i> = 0.048). <b><i>Conclusion:</i></b> Pretreatment CA199 is an independent factor for OS in patients with LARC with normal pretreatment CEA levels, which may reach the clinic to guide individualized decision-making.

scholarly journals The Elevated Pre-Treatment C-Reactive Protein Predicts Poor Prognosis in Patients with Locally Advanced Rectal Cancer Treated with Neo-Adjuvant Radiochemotherapy

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 780
Author(s):  
Richard Partl ◽  
Katarzyna Lukasiak ◽  
Eva-Maria Thurner ◽  
Wilfried Renner ◽  
Heidi Stranzl-Lawatsch ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
C Reactive Protein ◽  
Adjuvant Radiochemotherapy ◽  
Free Survival ◽  
Reactive Protein ◽  
Pre Treatment

The aim of the present study was to investigate the association of the pre-treatment C-reactive protein (CRP) plasma level with survival outcomes in a cohort of 423 consecutive patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy followed by surgical resection. To evaluate the prognostic value of the CRP level for clinical endpoints recurrence-free survival (RFS), local-regional control (LC), metastases-free survival (MFS), and overall survival (OS), uni- and multivariate Cox regression analyses were applied, and survival rates were calculated using Kaplan–Meier analysis. The median follow-up time was 73 months. In univariate analyses, the pre-treatment CRP level was a significant predictor of RFS (hazard ratio (HR) 1.015, 95% CI 1.006–1.023; p < 0.001), LC (HR 1.015, 95% CI 1.004–1.027; p = 0.009), MFS (HR 1.014, 95% CI 1.004–1.023; p = 0.004), and OS (HR 1.016, 95% CI 1.007–1.024; p < 0.001). Additionally, univariate analysis identified the MRI circumferential resection margin (mrCRM) and pre-treatment carcinoembryonic antigen (CEA) as significant predictor of RFS (HR 2.082, 95% CI 1.106–3.919; p = 0.023 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). Univariate analysis also revealed a significant association of the mrCRM (HR 2.089, 95% CI 1.052–4.147; p = 0.035) and CEA (HR 1.006, 95% CI 1.003–1.008; p < 0.001) with MFS. Age and CEA were prognostic factors for OS (HR 1.039, 95% CI 1.013–1.066; p = 0.003 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). In multivariate analysis that included parameters with a p-level < 0.20 in univariate analysis, the pre-treatment CRP remained a significant prognostic factor for RFS (HR 1.013, 95%CI 1.001–1.025; p = 0.036), LC (HR 1.014, 95% CI 1.001–1.027; p = 0.031), and MFS (HR 1.013, 95% CI 1.000–1.027; p = 0.046). The results support the hypothesis that an elevated pre-treatment CRP level is a predictor of poor outcome. If confirmed by additional studies, this easily measurable biomarker could contribute to the identification of patients who might be candidates for more aggressive local or systemic treatment approaches or the administration of anti-inflammatory drugs.

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