scholarly journals Efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for locally advanced rectal cancer

2020 ◽  
Author(s):  
Nobuki Imano ◽  
Yuji Murakami ◽  
Katsumaro Kubo ◽  
Daisuke Kawahara ◽  
Yuki Takeuchi ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Clinical Results ◽  
Tumor Stage ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Grade 3

Abstract Preoperative chemoradiotherapy with capecitabine or 5-fluorouracil is a standard treatment for locally advanced rectal cancer (LARC). S-1, a prodrug of 5-fluorouracil, is a candidate for this chemoradiotherapy regimen in Japan; however, treatment outcomes after S-1 treatment alone are not clear. This study aimed to assess the efficacy and tolerability of preoperative chemoradiotherapy with S-1 alone for LARC. We retrospectively evaluated 54 LARC patients who underwent preoperative chemoradiotherapy with S-1 alone in our institution between 2005 and 2017. The clinical tumor stage was cT2–3 in 31 patients and cT4 in 23 patients, and lymph node metastases were clinically evident in 31 patients. S-1, at a dose of 80 mg/m2/day, was orally administered during radiotherapy. A total dose of 45–50.4 Gy was delivered in 25–28 fractions (median: 50.4 Gy). Surgical resections were scheduled 6–10 weeks after chemoradiotherapy completion. The 3- and 5-year overall survival rates were 92.4 and 72.8%, respectively, with a median follow-up time of 51 months. The 3- and 5-year local control rates were 96.2 and 85.9%, respectively. A pathological complete response was observed in 7 patients (13.0%) at the time of surgery. Ten patients (18.5%) had grade 3 acute toxicities and 5 patients (9.3%) had grade 3 late toxicities. No grade 4 or 5 toxicities were observed. Preoperative chemoradiotherapy with S-1 alone followed by total mesorectal excision resulted in a low incidence of toxicities and comparable clinical results. Therefore, S-1 alone can be a treatment option for preoperative chemoradiotherapy in LARC patients.

Pilot Study of Patients’ Preferences for Immediate Resection Versus a Watch and Wait Approach After Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer

2020 ◽  
pp. OP.20.00158
Author(s):  
Ashray Gunjur ◽  
Grace Chazan ◽  
Genni Newnham ◽  
Sue-Anne McLachlan
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Survival Rates ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Recurrence Risk ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
Watch And Wait ◽  
Time Tradeoff

PURPOSE: In patients with rectal cancer who achieve a clinical complete response to neoadjuvant chemoradiation, it may be reasonable to adopt a watch-and-wait (W&W) strategy rather than proceed to immediate resection of the rectum. Patient preferences for this strategy are unknown. The primary aim of the current study was to determine the feasibility of assessing hypothetical recurrence and survival differences that relevant patients would tolerate to avoid immediate resection of the rectum. A secondary aim included estimating patients’ tolerance thresholds and the factors that might predict them. METHODS: We developed a study-specific written questionnaire based on a previously validated instrument. Hypothetical time tradeoff tasks were used to determine the recurrence rate patients would accept to adopt a W&W strategy and the survival benefit that would be needed to justify choosing immediate resection over W&W. Feasibility was measured on the basis of response rate, the stated ease of completion and the satisfaction of task, and time used. RESULTS: Twenty of 31 potentially eligible patients completed the study-specific questionnaire. The majority of respondents felt that questions were clear (70%) and not hard to understand (65%). The median acceptable recurrence risk to adopt a W&W strategy was 20% (interquartile range [IQR], 10%-35%). Patients required a median of 2.0 extra years of survival (IQR, 1.0-3.0 years) over a baseline 7.0 years, and they required a median extra 10% (IQR, 4%-19%) over baseline 70% survival rates to justify immediate resection. CONCLUSION: Measuring the preferences of patients with rectal cancer using time tradeoff methods seemed to be feasible. Larger studies are needed to confirm how acceptable a W&W strategy would be for relevant patients.

Phase Ib/II study of neoadjuvant chemoradiotherapy with CRLX101 and capecitabine for locally advanced rectal cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15144-e15144 ◽  
Author(s):  
Andrew Wang ◽  
Autumn Jackson McRee ◽  
A. William Blackstock ◽  
Bert H. O'Neil ◽  
Dominic T. Moore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Single Agent ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib ◽  
Grade 3

e15144 Background: There is strong interest in the development of novel agents to further improve the therapeutic ratio of neoadjuvant chemoradiotherapy for rectal cancer. CRLX101 is an investigational nanoparticle-drug conjugate with a camptothecin payload. The purpose of this Phase Ib/II study is to assess toxicity and to evaluate whether the addition of CRLX101 to chemoradiotherapy can improve pathologic complete response (pCR) for rectal cancer. Methods: This is a single-arm multicenter Phase Ib/II study examining the addition of CRLX101 to a standard capecitabine-based chemoradiotherapy regimen. Phase Ib employs a 3+3 dose escalation design with starting dose of 12 mg/m2 every other week (QOW). Dose level +1 was 15 mg/m2 (MTD for CRLX101 single agent QOW). Upon reaching MTD for QOW dosing, protocol was modified to evaluate QW CRLX101 dosing starting at 12 mg/m2 and 15 mg/m2as +1 level. Secondary endpoints included pCR and clinical outcome. Results: A total of 32 patients were enrolled on the trial. 26/32 had T3-4, 9/32 had N2 and 16/32 had N1 disease. For QOW dosing, 9 patients completed treatment without DLT and MTD was identified as 15 mg/m2 QOW. 14 patients were treated on the Phase II portion of the study at 15 mg/m2 QOW prior to the initiation of weekly dosing Phase Ib cohorts. For QW dosing, 0/3 patients experienced DLT at 12 mg/m2 and 1/6 patients experienced DLT at 15 mg/m2. The DLT was skin desquamation requiring treatment delay. QW MTD was identified as 15 mg/m2. Toxicities (all grade 3 except lymphopenia) that could possibly be attributed to CRLX101 are in Table 1. Full clinical and pathologic staging were available for 29/32 patients. Mean neoadjuvant rectal (NAR) score was 19 with standard deviation of 15. At the weekly MTD, 3/6 patients had pCR. Conclusions: CRLX101 weekly at 15 mg/m2+ standard capecitabine-based chemoradiotherapy appears to be well tolerated, with promising pCR rates that warrants further evaluation. A larger PhII trial should be considered with this regimen. Clinical trial information: NCT02010567. [Table: see text]

Exosomal microRNA-199b-5p as a potential circulating biomarker to predict response of preoperative chemoradiotherapy for locally advanced rectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15161-e15161 ◽  
Author(s):  
Dong Won Baek ◽  
Kyung Hwa Kim ◽  
Byung Woog Kang ◽  
Hye Jin Kim ◽  
Soo Yeon Park ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Serum Samples ◽  
Pathologic Stage ◽  
Tissue Specimens ◽  
Response Group

e15161 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision has become the standard treatment for locally advanced rectal cancer (LARC). However, the effect of CRT varies from complete response to complete resistance, and predicting response to CRT have not been well characterized yet. Previous studies have shown the potential of micro-RNA (miRNA) based approaches to enhance tumor radiation response. Accordingly, the present study attempted to identify biomarkers to predict response for preoperative CRT using comprehensive miRNA analysis in patients with LARC. Methods: This study included 65 rectal cancer tissues and 90 serum samples from patients who diagnosed with LACR and received preoperative CRT at Kyungpook National University Chilgok Hospital. Tissue specimens and serum samples were collected before CRT to evaluate the biologic differences between the good CRT response group and the poor CRT response group. For discovery of specific miRNAs, 800 miRNAs were analyzed using NanoString in 30 rectal cancer tissues. Thereafter, a total of 65 tissues, and 90 serum samples were investigated using real-time PCR for validation. Results: The median age was 59 years (range, 30-82), and the ratio of male to female was 3.05 to 1. The pathologic stages after preoperative CRT were as follows: pathologic complete response (n=13, 14.4%), pathologic stage I (n=13, 14.4%), pathologic stage II (n=27, 30.0%), pathologic stage III (n=28, 31.1%), and pathologic stage IV (n=9, 10.0%). In the discovery set, 16 target miRNAs were detected. In the validation set with tissue specimens, expression of 3 miRNAs (miR-199a/b-3p ( p=0.032), miR-199a-5p ( p=0.023), miR-199b-5p ( p=0.005)) was significantly upregulated which was associated with better response of CRT. Moreover, among the 3 candidate miRNAs, miR-199b-5p level was significantly upregulated in serum, and it was also found to be related with better response of CRT in LARC (pathologic stage 0/I versus II/III/IV, p=0.027). Conclusions: In the present study, high level of exosomal miR-199b-5p was associated with better response, suggesting it to be a promising non-invasive biomarker to predict response of CRT in patients with LARC. Accordingly, specific miRNAs can be predictive biomarker or therapeutic target to overcome radiotherapy resistance in LARC with a functional study.

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 Road to organ preservation in locally advanced rectal cancer

2017 ◽  
Vol 145 (7-8) ◽  
pp. 415-420
Author(s):  
Milica Nestorovic ◽  
Goran Stanojevic ◽  
Branko Brankovic
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Operative Management ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Pathological Examination ◽  
Diagnostic Tools ◽  
Non Operative Management

Introduction. In the past 20 years there has been significant change in the treatment of rectal cancer, especially in terms of multimodal approach. Surgery is, at least for now, the mainstay treatment for resectable rectal cancer. Preoperative chemoradiotherapy is, regardless of its modality, short or long course, different chemotherapeutic regiments, widely recommended for locally advanced rectal cancer. After neoadjuvant treatment, 15?27% of patients experience pathological complete response (pCR). These patients could benefit from non-operative management, thus avoiding potential surgical complications and possible reduction in the quality of life. Unfortunately, one cannot precisely define, while omitting surgery, which patients have pCR. For this reason Habr-Gama, a pioneer in the ?watch-and-wait? strategy, developed a new endpoint for non-operative management ? clinical complete response. To measure the response, in the absence of pathological examination, same diagnostic tools are used as in initial staging, but none is reliable enough to be used alone. This article is focusing on critical points in the reassessment of response to preoperative chemoradiotherapy for advanced rectal cancer, which is mandatory for appropriate selection of patients who might benefit from non-operative management.

scholarly journals Prognostic impact of acellular mucin pools towards the patients with locally advanced rectal cancer achieving pathological complete response after preoperative chemoradiotherapy

2020 ◽  
Vol 13 ◽  
pp. 175628482091125
Author(s):  
Lin Zhang ◽  
Huajie Guan ◽  
Qiuyun Luo ◽  
Lifang Yuan ◽  
Yulan Mao ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Pathological Complete Response ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Prognostic Impact

Background: To date, the prognostic significance of acellular mucin pools in tumors from patients with locally advanced rectal cancer (LARC) undergoing preoperative chemoradiotherapy (CRT) and subsequently obtaining pathological complete response (pCR) has not been well determined. Our current study aimed to explore the prognostic impact on these patients of acellular mucin pools. Methods: We collected clinical data from 117 consecutive LARC patients who achieved pCR after preoperative CRT and then underwent radical resection. Two groups of patients were generated, according to the presence or absence of acellular mucin pools. The 5-year disease-free survival (DFS) and overall survival (OS) rates were compared between the two groups of patients. Results: A total of 27 (23.1%) patients presented with acellular mucin pools. At a median follow-up period of 64 months, patients with acellular mucin pool showed a 5-year DFS rate (96.3% versus 83.7%, p = 0.110) and 5-year OS rate (100% versus 87.5%, p = 0.054) statistically similar to those of patients without acellular mucin pools. In univariable and multivariable Cox regression analyses, the presence of acellular mucin pools was not determined as an independent risk factor for DFS [hazard ratio (HR): 0.222; 95% confidence interval (CI): 0.029–1.864; p = 0.145] or OS (HR: 0.033; 95% CI: 0.000–9.620; p = 0.238). Conclusions: Acellular mucin pools had no significant prognostic impact on LARC patients showing pCR after preoperative CRT.

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