Effective Study of Preoperative Short-course Radiotherapy for the Advanced Resectable Rectal Cancer

Rectal Neoplasms Clinical Trial

Official title:

the Effect of the Preoperative Short-course Radiotherapy for the cT3/cN+ Mid-lower Rectal Cancer: a Prospective Randomized Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01437514
• Other study ID #: pSRT-201106
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: August 2011
• Est. completion date: December 2020

Study information

• Verified date: June 2021
• Source: West China Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The local recurrence of rectal cancer is one of the main problem that fail the treatment. The preoperative neoadjuvant (chemo)radiotherapy has been confirmed to reduce the local recurrence rate,especially in the advanced rectal cancer. However the local recurrence rate is low about 10-20% totally,and the integrity of the mesorectum after the operation and circumferential resection margin(CRM) are the most critical factor for the local recurrence.So that, the advanced rectal cancer patients with negative CRM and had a complete mesorectum excision,may not benefit from the neoadjuvant radiation.This trial was mainly focus on the resectable advanced rectal cancer patients whose preoperative stage was cT3/N+. These patients will be divided into the lower risk group and higher risk group according the preoperative CT,Endoscopic ultrasound, and MRI,and carrying out randomized trial in the two groups respectively.The purpose of this trial is to confirm whether the preoperative radiotherapy is necessary for all the advanced rectal cancer patients,identify the reason of the local recurrence,and finally help the making of the treatment decision for the advanced resectable rectal cancer.

Description:

The colorectal cancer is the secondary most common cancer among the population. Every year,it's estimated that there was over 1,200,000 new cases,and in China the data is about 440,000. The local recurrence (LR) and the lung or liver metastasis are the most critical problems that confusing the doctor,which the local recurrence rate is about 3%-50%,with a median rate of 18.8%。 Now, multidisciplinary treatment become a choice treatment for the rectal cancer, and the preoperative neoadjuvant (chemo)radiotherapy is a critical part of the treatment, as various trials have confirmed that the preoperative chemoradiotherapy can reduce the postoperative local recurrence rate. Although the preoperative radiotherapy can decrease the local recurrence, most of the studies show that it can't increase the overall survival. Also the large MRC study shows, the quality of operation is also critical for the local recurrence. and the main reasons of the local recurrence was thought to be the positive circumferential resection margin(CRM) and the remnant of the mesorectum. On the other hand, with the improvement of the TME surgery, the local recurrence of the advanced rectal cancer is lower than 20%, and the preoperative radiation may benefit half of these patients,and reduce the local recurrence rate to 7-10%.over 80% patients may be over treated and simultaneously suffer from the adverse effect of the radiation.The aim of this study was to explore that if the lower risk portion of the advanced rectal cancer patients is not necessary to have preoperative radiation,and the radiation will benefit the higher risk group.

In the trial,the operator will divide the resectable advanced rectal cancer patients (cT3/N+) into two subgroups according to the preoperative CT, MRI and EUS.firstly, the criteria of the lower risk group are: the tumor invade into the mesorectum<=5mm in lateral and posterior of the mesorectum, in the anterior wall the tumor had not invaded into the mesorectal fat tissue, there is no enlarged lymph node that larger than 8mm; and the higher risk group are: the tumor invade into the mesorectum >5mm in the lateral or posterior part, or invade into the mesorectum only in the anterior as the anterior mesorectum is relatively thin, or with lymph node larger than 8mm. then these patients were randomized to radiation with surgery or surgery only respectively. In the lower risk group we presume that the local recurrence rate is relatively low and the radiation can not improve LR, and in the higher risk group the radiation is significantly beneficial.

Of the preoperative radiation,there are two regimen,the long-term chemoradiotherapy and the short-course radiotherapy. mostly, the long-term regimen is more popular,with a total dose of 50.4 Gy in 25-28 fraction,compare to the short-term one with a dose of 25 Gy in 5 fraction, as the long-term regimen has a better effect of reduce the tumor invasion. For the resectable patients with negative CRM before the surgery,there is no conclusion which is better. so that the short-term radiation was choose as the regimen of this study.

Local recurrence after 3 years follow up has been chosen as primary endpoint. Proving a two-sided hypothesis of differences between the arms in higher risk group, the calculation of the sample size was based on expected local recurrence rates of 6% in the radiation group compared with 16% in the surgery group, resulting in altogether 210 patients (Log-Rank-test, with error of the 1st kind: α = 5% two-sided, power = 80%). As the lower risk group may have a very low LR rate, the totally 200 lower risk patients are planning to recruiting to randomization, which was similar to the higher risk group.

Patient baseline characteristics and disease factors were summarized using descriptive statistics. The categorical parameters were compared using two-sided Pearson's χ2 test or Fisher's exact test, as appropriate. All summary statistics on time-to-event variables were calculated according to the Kaplan-Meier method and were compared by means of the log-rank test. SPSS software(version 22.0; IBM, Chicago, IL) was used for statistical analyses. A P value<0.05 was considered significant.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 410
• Est. completion date: December 2020
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. histologically verified adenocarcinoma of the rectum;

2. the lower border of the tumor within 10cm of the anal verge;

3. age between 18 to 80 years;

4. preoperative endosonography,MRI and the abdominopelvic CT diagnosis as advanced rectal cancer (cT3/N+)(the detail of these two subgroup was illustrated in the detailed description of this trial);

5. ECOS = 2

6. there was no evidence of metastasis with chest and abdominopelvic CT.

Exclusion Criteria:

1. with other colorectal cancer, or other cancer,simultaneously;

2. Locally recurrent rectal cancer;

3. had a history of malignant tumor within 5 years(except the skin cancer);

4. Pregnant or lactating women

5. there was contraindication for the preoperative adjuvant radiotherapy or the operation.

6. with antitumor drug or radiation before this trial.

7. discovery of metastasis in the operation

8. worrying about the local recurrence or the adverse effect of the radiation excessively;

9. with mental disorder.

Related Conditions & MeSH terms

• Rectal Neoplasms

Intervention

Radiation:
• preoperative short-course radiotherapy
preoperative RT received a total dose of 25 Gy in five fractions during five consecutive days. The clinical target volume included the primary tumor and the mesentery with vascular supply containing the perirectal, presacral, and internal iliac nodes(up to the S1/S2 junction).The recommended upper border was at the level of the promontory. Radiation treatment was delivered with a three-portal technique.

Locations

Country	Name	City	State
China	Sichuan academy of medical science and sichuan provincial people's hospictal	Chengdu	Sichuan
China	the Third People'S Hospital of Chengdu	Chengdu	Sichuan
China	West China hospital, Sichuan University	Chengdu	Sichuan
China	The Third Affiliated Hospital of Kunming Medical University	Kunming	Yunnan

Sponsors (1)

Lead Sponsor	Collaborator
West China Hospital

Country where clinical trial is conducted

China, 

References & Publications (13)

Birgisson H, Påhlman L, Gunnarsson U, Glimelius B; Swedish Rectal Cancer Trial Group. Adverse effects of preoperative radiation therapy for rectal cancer: long-term follow-up of the Swedish Rectal Cancer Trial. J Clin Oncol. 2005 Dec 1;23(34):8697-705. — View Citation

Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005 Aug 20;23(24):5644-50. — View Citation

Frasson M, Garcia-Granero E, Roda D, Flor-Lorente B, Roselló S, Esclapez P, Faus C, Navarro S, Campos S, Cervantes A. Preoperative chemoradiation may not always be needed for patients with T3 and T2N+ rectal cancer. Cancer. 2011 Jul 15;117(14):3118-25. doi: 10.1002/cncr.25866. Epub 2011 Jan 24. — View Citation

Gu J, Wang L. [Standardized examination and research advancement of circumferential resection margin in patients with middle-lower rectal cancer]. Zhonghua Wei Chang Wai Ke Za Zhi. 2011 Apr;14(4):229-33. Chinese. — View Citation

Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. — View Citation

Kav T, Bayraktar Y. How useful is rectal endosonography in the staging of rectal cancer? World J Gastroenterol. 2010 Feb 14;16(6):691-7. Review. — View Citation

Korkolis DP, Plataniotis GD, Gondikakis E, Xinopoulos D, Koulaxouzidis GV, Katsilieris J, Vassilopoulos PP. Short-term preoperative radiotherapy is a safe approach for treatment of locally advanced rectal cancer. Int J Colorectal Dis. 2006 Jan;21(1):1-6. Epub 2005 Jun 10. — View Citation

Peeters KC, Marijnen CA, Nagtegaal ID, Kranenbarg EK, Putter H, Wiggers T, Rutten H, Pahlman L, Glimelius B, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. The TME trial after a median follow-up of 6 years: increased local control but no survival benefit in irradiated patients with resectable rectal carcinoma. Ann Surg. 2007 Nov;246(5):693-701. — View Citation

Pietrzak L, Bujko K, Nowacki MP, Kepka L, Oledzki J, Rutkowski A, Szmeja J, Kladny J, Dymecki D, Wieczorek A, Pawlak M, Lesniak T, Kowalska T, Richter P; Polish Colorectal Study Group. Quality of life, anorectal and sexual functions after preoperative radiotherapy for rectal cancer: report of a randomised trial. Radiother Oncol. 2007 Sep;84(3):217-25. Epub 2007 Aug 10. — View Citation

Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. doi: 10.1016/S0140-6736(09)60484-0. — View Citation

Stephens RJ, Thompson LC, Quirke P, Steele R, Grieve R, Couture J, Griffiths GO, Sebag-Montefiore D. Impact of short-course preoperative radiotherapy for rectal cancer on patients' quality of life: data from the Medical Research Council CR07/National Cancer Institute of Canada Clinical Trials Group C016 randomized clinical trial. J Clin Oncol. 2010 Sep 20;28(27):4233-9. doi: 10.1200/JCO.2009.26.5264. Epub 2010 Jun 28. — View Citation

Swedish Rectal Cancer Trial, Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7. Erratum in: N Engl J Med 1997 May 22;336(21):1539. — View Citation

van Gijn W, Marijnen CA, Nagtegaal ID, Kranenbarg EM, Putter H, Wiggers T, Rutten HJ, Påhlman L, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer: 12-year follow-up of the multicentre, randomised controlled TME trial. Lancet Oncol. 2011 Jun;12(6):575-82. doi: 10.1016/S1470-2045(11)70097-3. Epub 2011 May 17. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	local recurrence		3 years
Secondary	disease free survival	the time from operation to confirmed local recurrence, distant metastases, or death due to disease or treatment, whichever occurred first.	3 years
Secondary	metastatic rate	ratio of the patients with metastasis after the operation	3 years
Secondary	quality of life		3 years
Secondary	overall survival	the fraction of the person from the operation the death,no matter the reason of the death.	3 years
Secondary	short-term complication of the surgery		first 30 day after operation