Factors predictive of receiving neoadjuvant versus adjuvant chemoradiotherapy in locally advanced rectal cancer and the impact on overall survival.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 686-686
Author(s):  
Alex Richard Coffman ◽  
Dustin Boothe ◽  
Jonathan Evans Frandsen ◽  
Molly Gross ◽  
Thomas Bartley Pickron ◽  
...  

686 Background: Neoadjuvant chemoradiotherapy (NCRT) is generally accepted as the optimal treatment strategy compared to adjuvant chemoradiotherapy (ACRT) for locally advanced rectal cancer due to improvement in local control and reduced toxicity. However, NCRT has not been shown to improve overall survival (OS). We investigated the effect of NCRT versus ACRT on OS as well as the impact of demographic factors and clinical stage for the selection of each treatment approach utilizing the National Cancer Data Base. Methods: Adult patients with stage II and stage III adenocarcinoma of the rectum diagnosed from 2004-2013 were included. Chi-square analysis was used to compare demographic variables and clinical stage between the NCRT and ACRT treatment groups. Univariate and multivariate logistic regression modeling was used to identify factors predictive of each treatment strategy. Kaplan Meier and log-rank analysis along with propensity score matching was performed to determine the effect on OS. Results: A total of 20,262 patients were identified: 17,737 (87.5%) received NCRT and 2,525 (12.5%) received ACRT. Utilization of NCRT increased over the study period (p < 0.01). Factors associated with receipt of NCRT on multivariate analysis include: treatment at an academic institution (OR 0.76, 95% CI 0.68-0.85), income greater than $46,000 (OR 0.79, 95% CI 0.67-0.92), and living greater than 50 miles from a treatment facility. Factors associated with receipt of ACRT on multivariate analysis include: female sex (OR 1.12, 95% CI 1.01-1.24), Charlson comorbidity index of 1 (OR 1.18, 95% CI 1.04-1.34), and radiotherapy dose greater than 5040 centigray (OR 1.76, 95% CI 1.56-1.98). Compared to ACRT, NCRT was associated with a decreased risk of death on multivariate analysis (HR 0.91, 95% CI 0.84-1.00), which persisted after propensity score analysis. Conclusions: The use of NCRT for locally advanced rectal cancer is increasing and is associated with an OS benefit compared to ACRT.

2019 ◽  
Author(s):  
Minjun Zhang ◽  
Guangxian You ◽  
Hongen Xu ◽  
Tao Song ◽  
Haibo Zhang ◽  
...  

Abstract Objectives The relationship between total lymphocyte counts (TLCs) and survival is not well documented in rectal cancer. This study aimed to investigate the association between TLCs and disease-free survival (DFS) and identify factors associated with lymphopenia in locally advanced rectal cancer patients receiving chemoradiotherapy. Methods Thirty-six patients with locally advanced rectal cancer were retrospectively analyzed. TLCs were evaluated before surgery (pre-S), before radiotherapy (pre-RT), and during concurrent chemoradiotherapy (CCRT). The relationship between TLCs and DFS was analyzed by univariate and multivariate analysis. Potential clinical factors associated with lymphopenia were also evaluated. Results Median TLC declined significantly during radiotherapy. Severe lymphopenia during CCRT was significantly associated with poorer DFS on Kaplan-Meier analysis (p=0.01), univariate regression analysis (p=0.036), and multivariate regression analysis (p=0.038). Pre-S TLCs (p=0.009) and pre-RT TLCs (p=0.042) were significantly associated with severe lymphopenia on univariate regression analysis; however, only pre-S TLCs (p=0.026) were significantly associated with severe lymphopenia on multivariate regression analysis. Conclusions Severe lymphopenia was a predictor of poorer DFS in patients with locally advanced rectal cancer receiving adjuvant chemoradiotherapy. Pre-S TLCs were predictors of severe lymphopenia. Further study is warranted to reduce the rate of severe lymphopenia.


Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2071
Author(s):  
Jihane Boustani ◽  
Valentin Derangère ◽  
Aurélie Bertaut ◽  
Olivier Adotevi ◽  
Véronique Morgand ◽  
...  

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.


2011 ◽  
Vol 29 (20) ◽  
pp. 2773-2780 ◽  
Author(s):  
Carlo Aschele ◽  
Luca Cionini ◽  
Sara Lonardi ◽  
Carmine Pinto ◽  
Stefano Cordio ◽  
...  

Purpose To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.


2020 ◽  
Vol 1 ◽  
pp. 100012
Author(s):  
Joanna Gotfrit ◽  
Tharshika Thangarasa ◽  
Shaan Dudani ◽  
Rachel Goodwin ◽  
Patricia A. Tang ◽  
...  

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3571-3571 ◽  
Author(s):  
Mercedes Martinez Villacampa ◽  
Jaume Capdevila ◽  
Jose Luis Manzano ◽  
Carles Pericay ◽  
Ramon Salazar ◽  
...  

3571 Background: The addition of bevacizumab (BEV) to capecitabine (CAP)-based chemoradiation (CRT) has shown encouraging efficacy in locally advanced rectal cancer (LARC), in nonrandomized studies. This randomized phase II study investigated the effect of adding BEV to preoperative CAP-based CRT in patients (pts), with LARC. Methods: The primary end point was pathologic complete response (pCR). A two-stage design was used. Assuming a minimum pCR rate of at least 15% in one of the arms, a difference between the two arms of 10%, and accepting a probability of correct selection of 87%, 41 pts per arm were needed. Patients with LARC (Stages II-III assessed by MRI) and ECOG PS <2 were randomized to concurrent radiotherapy 45Gy/25f/5 weeks + CAP (825mg/m²/bid) + BEV every 2 weeks (5 mg/kg for 3 doses) (arm A) or the same schedule without BEV (arm B). Surgery was scheduled 6-8 weeks after completing CRT. Results: 90 pts were randomized (arm A/B: 44/46). Patient’s characteristics were well balanced between both arms: male 61%, median age 62 years, median distance from anal verge 7 cm, T3 79%, N+ 87%. 40 (91%)/43 (93%) of pts (arm A/B) finalized the planned CRT + surgery treatment. Overall grade 3-4 toxicity rates were 18 % and 13% (arm A/B, p=0.50); no grade 3-4 hematological toxicity was reported. Postoperative complications were 19(43%)/17(37%)(arm A/B). Efficacy data on patients who actually underwent surgery are reported in the table. Conclusions: The addition of BEV to CAP-based preoperative CRT has shown to be feasible and safe in the local control of LARC. No differences in pCR were observed and longer follow-up is needed to assess the impact on survival endpoints. [Table: see text]


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