scholarly journals Neoadjuvant chemotherapy in the combination treatment for locally advanced rectal cancer: currently available options

2018 ◽  
Vol 8 (3) ◽  
pp. 36-41
Author(s):  
D. V. Kuzmichev ◽  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
Zh. M. Madyarov ◽  
S. I. Tkachev ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Complete Clinical Response ◽  
Consolidation Chemotherapy ◽  
Group 3 ◽  
Group 2 ◽  
Grade Iii ◽  
Group 1

Objective:to analyze treatment outcomes in patients with locally advanced rectal cancer that received various combinations of neoadjuvant chemotherapy and chemoradiotherapy.Materials and methods. In this retrospective study, we analyzed a cohort of prospectively recruited patients with stage mrT3(CRM+)/ T4N0–2M0 locally advanced rectal cancer. Participants were divided into three groups. Patients in Group 1 received preoperative longcourse radiotherapy given concurrently with capecitabine, followed by 2–6 cycles of consolidation chemotherapy with capecitabine and oxaliplatin (CapOx). In Group 2, patients initially received 1–2 cycles of induction chemotherapy with CapOx, followed by radiotherapy + capecitabine, and then consolidation chemotherapy with CapOx (“sandwich” method). Participants in Group 3 were treated with 1–3 cycles of induction CapOx chemotherapy with subsequent long-course chemoradiotherapy. After the combination treatment, all patients underwent surgery. The primary endpoint of this study was therapeutic pathomorphosis. Secondary endpoints included complete clinical response, toxicity, local recurrence, distant metastasis, and relapse-free survival.Results.This study included 155 patients (98 in Group 1, 44 in Group 2, and 13 in Group 3). Grade III toxicity was documented in 6.12 %, 4.55 %, and 23.08 % of cases in Groups 1, 2, and 3 respectively. None of the patients had grade IV toxicity. Grade III therapeutic pathomorphosis was achieved in 33.7 %, 22.7 %, and 23.1 % of patients in Groups 1, 2, and 3 respectively. Grade IV therapeutic pathomorphosis was observed in 14.3 %, 15.9 %, and 7.69 % of patients in Groups 1, 2, and 3 respectively. Complete clinical response was registered in 16.3 %, 11.4 %, and 0 % of cases in Groups 1, 2, and 3 respectively. Median follow-up was 47.2 months with no signs of progression. Relapses were observed in 1.02 % and 2.27 % of patients from Group 1 and Group 2 respectively, whereas Group 3 demonstrated no relapses. A total of 11.22 %, 13.64 %, and 23.1 % of participants from Groups 1, 2, and 3 respectively developed distant metastasis.Conclusion.Polychemotherapy used within the consolidation and «sandwich» treatment regimens is a promising option for the treatment of locally advanced rectal cancer. The efficacy of induction chemotherapy should be further studied with a larger sample.

scholarly journals Quality of Life in a Randomized Trial Comparing Two Neoadjuvant Regimens for Locally Advanced Rectal Cancer – INCAGI004.

2021 ◽  
Author(s):  
Rodrigo Otavio de Castro Araujo ◽  
Fernando Meton Vieira ◽  
Ana Paula Victorino Ornellas ◽  
Claudia Carrada Torres ◽  
Ivanir Martins ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Rectal Resection ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Sphincter Preservation ◽  
Treatment Groups ◽  
Group 2 ◽  
Group 1

Abstract Background: Neoadjuvant chemoradiotherapy (neoCRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC), but the emergence of different drug regimens may result in different response rates. Good clinical response translates into greater sphincter preservation, but quality of life (QOL) may be impaired after treatment due to chemoradiotherapy and surgical side effects. Objective: To prospectively evaluate the QOL in a randomized trial comparing two neoadjuvant regimens for locally advanced rectal cancer.Methods: Stage II and III rectal cancer patients were randomized to receive neoCRT with either capecitabine (Group 1) or 5-Fu and leucovorin (Group 2) concomitant to long course radiotherapy. Clinical downstaging was accessed using MRI 6-8 weeks after treatment. EORTCs QLQ C30 and CR38 were applied before treatment (T0), after neoCRT (T1), after rectal resection (T2), early after adjuvant chemotherapy (T3), and one year after end of treatment or stoma closure (T4). Wexner scale was used for continence evaluation at T4. A C30SummaryScore (Geisinger et cols) was calculated to compare QOL results. Results: 32 patients were assigned to Group 1 and 31 to Group 2. Clinical downstaging occurred in 70.0% of Group 1 and 53.3% of Group 2 (p=0.288). pCR was 23.3% in group 1 and 10.0% in Group 2(p=0.165). Sphincter preservation was 83.3% in Group 1 and 80.0% in Group 2(p=0.111). No difference in QOL was detected comparing the two treatment groups before and after neoCRT. C30SummaryScore detected improvement comparing T0 to T1 and deterioration comparing T1 to T2 (p=0.025), and global health status improved at T1 and T4 compared to T0(p=0.004). Mean Wexner scale score was 9.2, and a high score correlated with symptoms of diarrhea and defecation problems at T4.Conclusions: Clinical and pathological response rates were equivalent in both treatment groups. QOL was improved after neoCRT corresponding to clinical response but decreased following rectal resection. Wexner score was high after sphincter preservation. C30SummaryScore was a useful tool to detect differences in overall QOL in EORTCs multiple item questionnaire.Trial registration: NCT03428529. Registered 02/09/2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03428529.

Relations of changes in serum carcinoembryonic antigen (CEA) levels before and after chemoradiotherapy (CRT) and after surgery to histological response and outcomes in patients with locally advanced rectal cancer (LARC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 804-804
Author(s):  
Gota Saito ◽  
Sotaro Sadahiro ◽  
Hiroshi Miyakita ◽  
Kazutake Okada ◽  
Akira Tanaka ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Histological Response ◽  
Group 4 ◽  
Positive Serum ◽  
Serum Cea ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

804 Background: Multidisciplinary treatment had been a standard of care for locally advanced rectal cancer. Serum CEA had been reported as one of the predictive factors to CRT, however, serum CEA levels may change after CRT and surgery. We examined the relations of serum CEA before CRT, after CRT, and after surgery to histological response and outcomes. Methods: The subjects were 149 patients with cStage II or III adenocarcinoma of the rectum who underwent surgery after CRT from 2005 through 2013. A total dose of 40 to 45 Gy with concurrent oral UFT or S-1 was delivered. Surgery was performed 6 to 8 weeks after CRT. A serum CEA > 5 ng/mL was defined as positive. Patients with negative serum CEA before CRT were designated as group 1. Patients with positive serum CEA before CRT that became negative after CRT were designated as group 2. Patients with positive serum CEA after CRT that became negative after surgery were designated as group 3, and patients with positive serum CEA after CRT as well as after surgery were designated as group 4. The median follow-up period of the survivors was 60.4 months. Results: The numbers of patients in Groups 1, 2, 3, and 4 were 55 (37%), 41 (28%), 37 (25%), and 16 (11%), respectively. The incidences of pCR, T downstaging, and N downstaging did not differ significantly among the groups (p = 0.094, 0.060, and 0.346). Rates of marked regression (TRG Grade 1 or 2) were 55% in Group 1, 42% in Group 2, 16% in Group 3, 25% in group 4. The rates were significantly higher in groups 1 and 2 (p = 0.001).5y DFS was 76% in group 1, 75% in group 2, 77% in group 3, and 48% in group 4 and was significantly lower in group 4 (p = 0.024). 5y OS was 88% in group 1, 91% in group 2, 85% in group 3, and 68% in group 4 and was significantly lower in group 4 than that in groups 1 and 2 (p = 0.03, 0.019). Conclusions: In patients with rectal cancer who received CRT, changes in serum CEA levels before and after CRT and after surgery were intimately related to the histological response of the primary lesion. Patients who continued to have positive serum CEA levels after surgery had poor outcomes, strongly suggesting the presence of occult distant metastasis.

Impact of time to surgery in locally advanced rectal cancer patients.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 719-719
Author(s):  
Madiha Naseem ◽  
Manwah Yeung ◽  
Suruthi Senthilvel ◽  
Pooya Dibajnia ◽  
Doshina Naila ◽  
...  
Keyword(s):  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Time To Surgery ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Statin Use ◽  
Group 1

719 Background: Patients with locally advanced rectal cancer (LARC) undergo surgery at 6-8 weeks after neoadjuvant chemoradiation based on standard protocol. However, the optimal time to undergo surgery remains debatable. The goal of this study was to identify associations between time to surgery and additional variables with overall survival (OS) and recurrence rates in LARC patients. Methods: A retrospective chart review was conducted for 80 LARC patients with T3 or node positive disease, who have undergone neoadjuvant chemoradiation and surgery at St. Michael’s Hospital from January 1st 2005-December 31st 2015. Patients were divided into 4 groups based on time to surgery: 4-6 weeks (group 1), 6-8 weeks (group 2), 8-10 weeks (group 3), and > 10 weeks (group 4). Cox proportional hazards model was used to find associations with recurrence and OS. Results: Of the 80 patients, 67.5% (n = 54) were male and 32.5% (n = 26) were female. Median age at diagnosis was 59 years (range, 28-80 years). Median follow-up was 4.84 years. Recurrence occurred in 29% (n = 23) of patients. Incidence of death was 11% (n = 9). Pathologic complete response (pCR) was achieved in 15% (n = 12) of patients. Statin use during chemoradiation was prevalent in 25% (n = 20) of patients. Compared to group 1, patients in group 2 had a 14% reduction in the risk of recurrence (hazard ratio (HR): 0.86, 95% CI: 0.252.91); group 3 had a 69% reduction (HR: 0.31, 95% CI: 0.081.22) and group 4 had a 55% reduction (HR: 0.45, 95% CI: 0.073.08). There was no statistically significant difference in OS between the 4 groups. Furthermore, patients who took statins during chemoradiation had improved OS (HR: 5.42, 95% CI: 39.27.48, p < 0.019) with no difference in pCR rate. Conclusions: This study shows that surgery at 8-10 weeks after chemoradiation offers the best disease-free survival outcome. It also highlights a mortality benefit conferred by statin use during chemoradiation. This could be attributed to the radiosensitizing effects of statins, which allow tumor stem cells to undergo enhanced autophagy. Further prospective studies are warranted to investigate this therapeutic benefit.

Outcomes of Neoadjuvant Chemotherapy without Radiation for Rectal Cancer

2015 ◽  
Vol 32 (4) ◽  
pp. 275-283 ◽  
Author(s):  
Takuya Matsumoto ◽  
Suguru Hasegawa ◽  
Masazumi Zaima ◽  
Naoya Inoue ◽  
Yoshiharu Sakai
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Short Term ◽  
Group 2 ◽  
Grade 3

Aim: The efficacy of neoadjuvant chemotherapy without radiation (NAC) in the treatment of rectal cancer remains unclear. This retrospective study was aimed at determining the pathological complete response rate and short-term outcomes of NAC in patients with locally advanced rectal cancer. Patients and Methods: We collected data on 159 consecutive patients treated for rectal cancer (cT3/cT4a, cN+, and cM0 status) at five tertiary referral hospitals between 2005 and 2010. Pathological complete response (pCR) and safety were assessed as the main outcomes in 124 eligible patients comprising 15 who received NAC (NAC group) and 109 who received no neoadjuvant chemotherapy (non-NAC group). Results: In the NAC group, 2 patients (13.3%) achieved a pCR (95% confidence interval: 1.7-40.5%) and 3 patients (20%) experienced grade 3/4 adverse events. No significant differences were found between the NAC and non-NAC groups in terms of short-term outcomes, including R0 proportion (100 vs. 96.3%, p = 0.45) and postoperative grade 3/4 complications (13.3 vs. 18.4%, p = 0.63). Conclusions: Neoadjuvant systemic chemotherapy without radiation appears to be safe, without worsening short-term outcomes, in patients with locally advanced rectal cancer. A further study is needed to verify these findings in larger samples.

scholarly journals Adding Three Cycles of CAPOX after Neoadjuvant Chemoradiotherapy Increases the Rates of Complete Response for Locally Advanced Rectal Cancer

2021 ◽  
Vol 28 (1) ◽  
pp. 283-293
Author(s):  
Zhiwei Zhai ◽  
Kunning Zhang ◽  
Chen Wang ◽  
Tian Zhang ◽  
Lixia Wang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Distant Metastases ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Consolidation Chemotherapy ◽  
Significant Difference

Background and Objectives: the total neoadjuvant chemoradiotherapy (TNT) includes different strategies, but the most appropriate model remains uncertain. The purpose of this retrospectively study was to evaluate the safety and pathological response in the consolidation chemotherapy model. Methods: patients with cT3/T4 or TxN + M0 rectal cancer that were receiving neoadjuvant chemoradiotherapy (CRT) (50 Gy with oral capecitabine)/TNT (CRT followed by three cycles of CAPOX) during September 2017 to September 2019 in our department were included. All of the patients were recommended to receive radical surgery. Results: a total of 197 patients were included. Eighty-one patients received CRT, while one hundred and sixteen patients received TNT. Nine patients did not undergo surgery because of the distant metastases (one patient (1.2%) in CRT group, two patients (1.7%) in TNT group) or a refusal of resection (two patients in CRT group, four patients in TNT group). The pathological complete response (pCR) rate was 32.7% in TNT compared with 12.8% in CRT (p = 0.002). There was no statistically significant difference in grade 3 acute toxicities of neoadjuvant treatment and surgical complications between the two groups. Conclusions: the consolidation chemotherapy model is safe for patients with locally advanced rectal cancer and it has a high pCR rate. The long-term follow-up is necessary to be evaluated in a future prospective, randomized trial.

Oxaliplatin and capecitabine initially concomitant to radiotherapy then administered in the resting period in high-risk locally advanced rectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 581-581
Author(s):  
Pei-Rong Ding ◽  
Yuan-Hong Gao ◽  
Xin An ◽  
Gong Chen ◽  
Feng-Hua Wang ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Radiation Dermatitis ◽  
Consolidation Chemotherapy ◽  
Grade 3 ◽  
The Impact ◽  
Resting Period

581 Background: Although neoadjuvant chemoradiotherapy (CRT) has dramatically reduced the risk of local recurrence in locally advanced rectal cancer (LARC), it fails to reduce the risk of systemic failure. To enhance systemic control, we develop an alternative approach, combining intense chemotherapy using Oxaliplatin and Capecitabine (XELOX regimen) concomitant to radiation and extending the chemotherapy regimen to the resting period (consolidation chemotherapy) for high risk LARC. The aim of the present study was to evaluate the efficacy and toxicities of this strategy. Methods: Patients with high risk LARC were treated with CRT. Two cycles of XELOX regimen was administered concomitant to radiation. Then an additional cycle of the same regimen was extended to the resting period one week after completion of chemoradiation. Tumor response, toxicities associated with CRT and consolidation chemotherapy, and surgical complications were recorded. Results: Thirty-six patients with high risk LARC were identified treated with the strategy from 2010 to 2012. All patents completed the planned dose of radiation and concurrent chemotherapy, and two patient was unable to complete the consolidation chemotherapy because of grade 3 toxicities. Grade 3 acute toxicities were 2.8% leucopenia, 2.8% diarrhea, and 2.8% radiation dermatitis. All patients underwent optimal surgery with TME, among whom sphincter-saving procedure was performed in 27 patients (75%). There was no peri-operative mortality in this cohort. Seven patients (19.4%) developed postoperative complications. Complete regression (pCR), major regression (nearly pCR), and moderate or minimal regression were achieved in 13 (36.1%), 16 patients (44.4%), and 7 patients (19.5%), respectively. Conclusions: The preliminary results suggest that XELOX regimen concomitant to radiation and extended to the “resting period” after radiation completion are well tolerated. This strategy is associated with high pCR and nearly pCR rates. The promising results warrant further investigation of the impact of consolidation chemotherapy following CRT for LARC in future clinical trials.

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