Indications for neoadjuvant treatment based on risk factors for poor prognosis before and after neoadjuvant chemotherapy alone in patients with locally advanced rectal cancer

Author(s):  
Atsushi Ogura ◽  
Kay Uehara ◽  
Toshisada Aiba ◽  
Masanori Sando ◽  
Aya Tanaka ◽  
...  
2020 ◽  
Author(s):  
Zechuan Jin ◽  
Du He ◽  
Yu Shen ◽  
Xiangbing Deng ◽  
Ziqiang Wang

Abstract Background: For patients with locally advanced rectal cancer, side effects such as nausea, vomiting and loss of appetite may occur during neoadjuvant chemotherapy, but small intestinal perforation is very rare.Case presentation: We present a case of a 62-year-old man who suffered small intestinal perforation in the first cycle neoadjuvant treatment of locally advanced rectal cancer with capecitabine and oxaliplatin. Six days after the start of neoadjuvant chemotherapy, he began to develop intermittent abdominal pain, accompanied by diarrhea and abdominal distension. The CT scan revealed an abscess with free air in the pelvic cavity with proximal intestinal ileus. Then we performed a laparotomy. After enterolysis, the rectum with tumor was carefully examined with no perforative lesion, and the terminal ileum about 15cm from the ileocecum which adhere to the pelvic abscess had one about 0.8cm ulcer. The patient had a radical anterior resection and the morbid small bowel resection with protective ileostomy. The postoperative pathological examination showed the full-thickness necrosis of the intestinal wall in the ileal lesion with peripheral acute suppurative inflammation. AND the final pathological stage of the tumor was pT3N0M0 (American Joint Committee on Cancer, eighth edition).Conclusion: As a chemotherapy regimen based on fluorouracil and oxaliplatin, small intestinal perforation is a very rare complication. The most common complications of these two drugs are gastrointestinal symptoms such as diarrhea. Therefore, when the complications are not relieved during chemotherapy, we should think of a more serious possibility.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 615-615 ◽  
Author(s):  
Yanhong Deng ◽  
Jianwei Zhang

615 Background: The incidence of Mismatch repair gene deficiency (dMMR) was about 15% in colorectal cancer, but mostly in right side colon cancer, while in locally advanced rectal cancer, it is very rare. As is known, adjuvant chemotherapy with 5FU alone was not recommended in stage II colon cancer with dMMR or MSI. However, in locally advanced rectal cancer with dMMR or MSI, the efficacy of neoadjuvant treatment with 5FU was not yet known. Methods: We enrolled patients with locally advanced rectal cancer from three prospective clinical trials, including the FOWARC study (N = 309), the mFOLFOXIRI neoadjuvant chemotherapy trial (N = 106) and the total neoadjuvant treatment with FOLFOX and radiotherapy (N = 129). From the 544 patients, 35 (6.4%) patients were dMMR, 133 patients with unknown status of MMR. Among the 35 patients, 10 patients received 5FU concurrent with radiotherapy (group A), nine patients underwent FOLFOX concurrent with radiation (group B), and 12 patients received FOLFOX neoadjuvant chemotherapy alone (group C). Another four patients underwent mFOLFOXIRI neoadjuvant chemotherapy alone (group D), including one patient with nivolumab as neoadjuvant treatment after chemotherapy. Results: Totally, 4 (11.4%) patients achieved pathologic complete response, and 13 (37%) patients had tumor downstaging to ypT0-2N0M0 (stage 0-I). In group A, the pCR rate was 10% (1/10), the tumor downstaging rate was 20% (2/10); In group B, the pCR rate was 33.3% (3/9), the tumor downstaging rate was 55.6% (5/9); In group C, the tumor downstaging rate was 41.7% (5/12). In group D, only one patient achieved pCR, and it is the one who received nivolumab as neoadjuvant treatment. Conclusions: The efficacy of neoadjuvant in locally advanced rectal cancer seemed not affected by the MMR status. But further study was needed.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keisuke Miwa ◽  
Eiji Oki ◽  
Masanobu Enomoto ◽  
Keisuke Ihara ◽  
Koji Ando ◽  
...  

Abstract Background Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT. Methods Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety. Results From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9–83.6) and 73.4% (95% CI 58.7–83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414–1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable. Conclusion We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases. Trial registration Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J


2020 ◽  
Author(s):  
Keisuke Miwa ◽  
Eiji Oki ◽  
Masanobu Enomoto ◽  
Keisuke Ihara ◽  
Koji Ando ◽  
...  

Abstract BackgroundPreoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT. MethodsPatients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.ResultsFrom September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9–83.6) and 73.4% (95% CI 58.7–83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414–1.578). The 3-year survival rates were 92.3% and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5% and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable. ConclusionWe demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.Trial registrationThis study was registered in the UMIN clinical trials registry on Aug 14th, 2013. (UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.


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