Association of adjuvant chemotherapy with improved overall survival for patients with locally advanced rectal cancer (LARC) who achieve a pathologic complete response (pCR) to neoadjuvant chemoradiation (nCRT).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 716-716
Author(s):  
Danish Shahab ◽  
Emmanuel M. Gabriel ◽  
Kristopher Attwood ◽  
Valerie Francescutti ◽  
Wen Wee Ma ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Comorbidity Score ◽  
N Stage

716 Background: 15-20% of patients with locally advanced rectal adenocarcinoma (LARC) achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation (nCRT). The role of adjuvant chemotherapy has been questioned. Methods: Patients with rectal cancer receiving nCRT in the National Cancer Data Base (NCDB) 2006-2013 data set were evaluated. The primary outcome was overall survival (OS). The association between OS and patient characteristics were examined using multivariable Cox regression models. Results: 2,903 patients were identified who achieved a pCR. The median follow up was 43.2 months. 2,102 received nCRT and 789 received nCRT + adjuvant chemotherapy. Factors significantly associated with OS included age (p<0.001), gender (p=0.011), Charlson-Deyo comorbidity score (CDI) (p<0.001), grade (p=0.029), clinical T stage (p=0.030), and CEA negativity (p=0.002), but not nodal status. The 3-year OS rate was 94% in the adjuvant therapy group as compared to 84% in the nCRT alone group (p<0.001). In considering clinical N-stage, the benefit was comparable for both N+ and N- tumors. Adjuvant chemotherapy was more likely to be given for younger patients (age < 60), lower comorbidity score, higher grade, positive CEA status, higher clinical T stage, and higher clinical N stage. When stratifying by these factors, similar benefits in OS were observed in the adjuvant cohort. Conclusions: Following nCRT and achievement of a pCR, the receipt of adjuvant chemotherapy is associated with improved OS. Patients receiving adjuvant therapy were more likely to be younger and have a low CDI, but have more advanced stage disease. Thus, a selection bias may be present. Nonetheless, in the setting of the already excellent outcome associated with pCR, the additional benefit of adjuvant chemotherapy should be weighed against toxicity.

Effect of adjuvant chemotherapy following pathologic complete response on long-term survival in rectal cancer: A propensity score matched analysis.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 717-717 ◽  
Author(s):  
Ali Mokdad ◽  
Sergio Huerta ◽  
Rebecca M Minter ◽  
John C. Mansour ◽  
Michael A. Choti ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Clinical Stage ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Term Survival

717 Background: The role of adjuvant chemotherapy following resection in patients with rectal cancer that achieve pathologic complete response (pCR) after neoadjuvant therapy is unclear. Current data have been limited by small sample size series. This study examined the impact of adjuvant chemotherapy following pCR on overall survival in a national cohort of patients. Methods: Patients with rectal adenocarcinoma were identified in the National Cancer Data Base between 2006 and 2012. Those with locally advanced tumor (clinical stage II or III) that achieved pCR (defined as ypT0N0 in surgical specimens) after neoadjuvant chemoradiotherapy (nCRT) were included in the study. We matched by propensity score patients that received adjuvant chemotherapy (ACT) and patients that did not receive postoperative treatment (no-ACT) controlling for demographic as well as perioperative patient and tumor characteristics. Overall survival was compared using a Cox proportional hazards model. Results: We identified 2,543 patients (ACT: 732, no-ACT: 1,811 patients) with resected locally advanced rectal adenocarcinoma that achieved pCR after nCRT. Among patients that received ACT, 711 were matched with 711 patients in the no-ACT group. Adjuvant chemotherapy was associated with improved overall survival compared to no-ACT (hazard ratio[HR] = 0.46, 95% confidence interval [CI] = 0.29 – 0.75). Overall survivals at 1, 3, and 5 years in the ACT and no-ACT groups were 100% vs 98% (P=0.1), 98% vs 94% (P<0.01), and 94% vs 89% (P<0.01), respectively. In subgroup analyses, adjuvant chemotherapy improved overall survival in patients with clinical stage II (HR = 0.43, 95% CI = 0.22 – 0.85) as well as stage III tumor (OR = 0.50, 95% CI = 0.26 – 0.98). Among patients that received adjuvant chemotherapy, there was no difference in overall survival between single agent and multiagent regimens (HR = 1.37, 95% CI = 0.57 – 3.29). Conclusions: Adjuvant chemotherapy may providea small long-term survival benefit in patients with resected locally advanced rectal cancer and pCR after nCRT.

Assessment of macroscopic features in relation to tumor response to neoadjuvant chemoradiation therapy in rectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 507-507
Author(s):  
Amanda Kathleen Arrington ◽  
Julio Garcia-Aguilar ◽  
Marjun Philip Duldulao ◽  
Carrie Luu ◽  
Julian Sanchez ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Response ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Oncologic Outcomes ◽  
Neoadjuvant Chemoradiation Therapy ◽  
Pathologic Features

507 Background: Several studies show locally advanced rectal cancer patients with clinical complete response (cCR) have comparable oncologic outcomes to pathologic complete response (pCR) to neoadjuvant chemoradiation therapy (NCRT). Thus, total mesorectal excision (TME) could potentially be avoided. Our objective was to validate macroscopic features of cCR. Methods: 164 patients with stage II/III rectal cancer were previously enrolled in a phase II trial and treated by NCRT and TME. Tumor response in the surgical specimens was assessed according to AJCC guidelines. A pCR was defined as absence of viable tumor cells. Gross macroscopic features by the pathologist were tabulated and our cohort was applied to previously published cCR criteria. Results: 25.0% (n = 41) had pCR; 75.0% (n = 123) had non-pCR. Descriptors were condensed into 14 macroscopic features by combining terms and excluding those rarely mentioned. Several reports affirm that scarring signifies cCR, while others suggest that fibrosis, edema, ulceration and nonpalpable tumor to be consistent with cCR. In our study, scarring was found in 6.1% of patients, 16.7% of which had pCR. We found that hyperemia, scarring, flat, smooth, and tan-pink mucosa were significantly associated with pCR (p < 0.05). In contrast, a firm lesion and ulceration were frequently observed in patients with non-pCR (p = 0.02 and 0.05 respectively). Conclusions: Our study suggests that macroscopic pathologic features do correlate with pCR. Although cCR has comparable oncologic outcomes as pCR with favorable outcomes, standard criteria of cCR should first be defined so NCRT patients can safely be selected for observation only. [Table: see text]

Induction chemotherapy followed by chemoradiotherapy and total mesenteric excision for locally advanced rectal cancer with resectable metastases.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
Carla Hajj ◽  
Andrea Cercek ◽  
Leonard Saltz ◽  
Neil Howard Segal ◽  
Diane Lauren Reidy ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Induction Chemotherapy ◽  
Primary Tumor ◽  
Tumor Regression ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

526 Background: Optimal management of patients with locally advanced rectal cancer (LARC) and synchronous, resectable metastases remains controversial and treatment decisions benefit from a multidisciplinary approach. To better characterize the role of induction chemotherapy followed by chemoradiation and surgery, we evaluated patterns of distal progression and overall survival in this subset of patients. Methods: We reviewed records of 25 LARC patients with synchronous resectable metastases treated with induction chemotherapy (ICT) followed by 5-fluorouracil-based concurrent chemoradiation (CRT) at our institution between December 2006 and December 2010. Radiation was delivered using a standardized three-field technique or IMRT. The incidence and sites of failure were analyzed. Overall survival (OS) and progression-free survival (PFS) were calculated from the completion of CRT using the Kaplan-Meier method. Results: Of the 25 patients who received ICT followed by CRT, 21 (84%) underwent total mesorectal excision and metastectomy. Eleven patients (44%) had liver metastases. The median ICT duration was 2.4 months. Twenty patients (80%) received a FOLFOX-based ICT regimen and 5 patients (20%) received irinotecan-based chemotherapy. Two patients had unresectable disease, one was medically inoperable, and surgery was aborted due to intra-operative complications in one patient. Eighteen of the 21 were NED after surgery and metastatectomy (86%) with 24% pathologic complete response rate in the primary tumor; 10 (56%) received adjuvant chemotherapy. None of the patients recurred locally. Six of the 18 (33%) progressed distally, four of whom had received adjuvant chemotherapy. Four distal recurrences were in the lungs. With a median follow-up of 29.6 months, the 3-year OS was 50.4%. Median OS and PFS were 25.1 months and 13.5 months, respectively. Conclusions: ICT prior to CRT is associated with acceptable toxicity, substantial primary tumor regression, and promising clinical outcomes in patients with high-risk LARC with synchronous, resectable metastatic disease.

Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single arm phase II study (FOTAC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. TPS816-TPS816
Author(s):  
Jianwei Zhang ◽  
Yue Cai ◽  
Huabin Hu ◽  
Jian Xiao ◽  
Dianke Chen ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase Ii Study ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Chemoradiation Therapy ◽  
Neoadjuvant Chemoradiation Therapy

TPS816 Background: Preoperative 5-Fluorouracil based chemoradiotherapy is the standard of treatment for locally advanced rectal cancer. About 15% to 18% of patients would achieve pathologic complete response (pCR) after 5-Fluorouracil based chemoradiation. And the survival outcome of patients with pCR was much better than that of non-pCR. In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that totally neoadjuvant chemoradiation therapy with mFOLFOX6 could improve the pCR rate from 18% to 45% with 5% type I error and 80% power. Fifty patients met inclusion criteria will be enrolled in the trial. All patients will receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before operation. Totally, the patients will receive 8-10 cycles of chemotherapy before surgery. MRI of the pelvic will be performed every 4 cycles of the therapy to assess clinical response. Then the patient will receive total mesorectal excision at least 8 weeks after radiotherapy. The post-operative chemotherapy will be omitted and all the patients go to surveillance. Clinical trial information: NCT02887313.

INNOVA: A phase II randomized study comparing INterval versus NeOadjuVAnt chemotherapy in magnetic resonance imaging-defined high risk rectal cancer.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. TPS879-TPS879
Author(s):  
Ramakrishnan Ayloor Seshadri ◽  
Trivadi S. Ganesan ◽  
Arunkumar M N ◽  
Shirley Sundersingh
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Rectal Cancers

TPS879 Background: Patients with rectal cancers treated with neoadjuvant chemoradiation followed by surgery and adjuvant chemotherapy are not exposed to systemic doses of chemotherapy until very late in the treatment schedule. Preoperative chemotherapy, either in the neoadjuvant or interval setting can lead to early treatment of micrometastasis, improve the tumor response and possibly the overall survival. Phase II studies of neoadjuvant chemotherapy in rectal cancer have shown good response to chemotherapy with no tumor progression and good compliance. A phase II study evaluating the effect of giving chemotherapy in the interval waiting period between chemoradiation and surgery has shown acceptable toxicity and high pathological complete response rates. Methods: This single centre, randomized, open label, phase II trial compares the safety and efficacy of two pre-operative regimens in locally advanced MRI defined high-risk rectal cancers. Based on the Simon optimal two-stage design, 94 patients will be randomised to either Arm A [3 cycles of neoadjuvant chemotherapy (capecitabine and oxaliplatin) followed by chemoradiation (50.4 Gy with capecitabine) and then surgery] or Arm B [neoadjuvant chemoradiation followed by 3 cycles of interval chemotherapy and then surgery]. Patients in both arms receive 3 cycles of adjuvant chemotherapy. The primary end-point is the pathological complete response rate. Secondary end-points include frequency and severity of adverse events, RO resection rates, tumor regression grading and compliance to treatment. The inclusion criteria: age 18 to 70 years; ECOG performance status 0-2; non-metastatic, locally advanced rectal cancer with any one of the following features on high-resolution thin slice MRI: any T3/T4 tumor in the lower rectum, T3c/T3d/T4 tumor in the mid rectum, N2 disease, threatened mesorectal fascia, or extramural vascular invasion. Patients are randomly assigned to one of the two intervention arms in a 1:1 ratio. Prespecified activity goal for the first stage of accrual was met; second stage accrual began in July 2017. Clinical trial information: CTRI/2015/01/005385.

Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: A National Cancer Database (NCDB) analysis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 616-616 ◽  
Author(s):  
Shaakir Hasan ◽  
Paul Renz ◽  
Rodney E Wegner ◽  
Gene Grant Finley ◽  
Moses S. Raj ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Microsatellite Instability ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
National Cancer Database

616 Background: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. We therefore utilized the national cancer database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. Methods: We analyzed 5,086 patients between 2010-2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4,450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional hazard ratios were used for survival. Results: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher grade tumors (P < 0.05). The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (OR = 0.65, 95% CI 0.43 – 0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared to 73% without it (< 0.001). Conclusions: Microsatellite instability was independently associated with a reduction in pathologic complete response for locally advanced rectal cancer following neoadjuvant chemoradiation in this NCDB-based analysis.[Table: see text]

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