Efficacy and Safety of Neoadjuvant Chemoradiotherapy Combined With PD-1 Inhibitor and Thymalfasin for Locally Advanced Mid-low Rectal Cancer: a Single-center, Retrospective, Controlled Study
Overview
- Phase
- Not Applicable
- Intervention
- Thymalfasin
- Conditions
- Colorectal Neoplasms
- Sponsor
- Beijing Friendship Hospital
- Enrollment
- 26
- Locations
- 1
- Primary Endpoint
- pathologic complete response
- Status
- Not yet recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
It is a single-center, retrospective, controlled study to investigate the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin for locally advanced mid-low rectal cancer.
Detailed Description
Study Purpose 1. To evaluate the efficacy and safety of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin for locally advanced mid-low rectal cancer. 2. To explore the effects of neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin on the immune microenvironment of locally advanced mid-low rectal cancer. Study Design: A single-center, retrospective, controlled study Subjects were divided into two groups according to whether or not they received thymalfasin: group 1 was treated with neoadjuvant chemoradiotherapy combined with PD-1 inhibitor, and group 2 was treated with neoadjuvant chemoradiotherapy combined with PD-1 inhibitor and thymalfasin. Subjects received long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5 weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent TME surgery (12-14 weeks). Thymalfasin was started on the first day of neoadjuvant chemoradiotherapy, 1.6 mg subcutaneously twice a week until the end of the last neoadjuvant treatment. Enrollment: 26 participants, 13 in each group Study Population: locally advanced mid-low rectal cancer Primary Endpoint: pathologic complete response（pCR） Exploratory endpoint: Paraffin specimens were collected from biopsies before neoadjuvant therapy and after surgery in patients meeting the inclusion criteria. The expression of CD86, CD163, CD4+T，CD8+T，PD-1 were detected.
Investigators
Zhongtao Zhang
professor
Beijing Friendship Hospital
Eligibility Criteria
Inclusion Criteria
- •Patients with rectal adenocarcinoma must satisfied all the following conditions:
- •Stage II/III LARC (cT1-4aN0-2M0);
- •Tumor distal location≤10 cm from anal verge (MRI diagnosed);
- •Patients regardless of gender with aged≥18 years
- •ECOG score of 0 or 1
- •Physical and viscera function of patients can withstand major abdominal surgery
Exclusion Criteria
- •Current or previous active malignancy other than rectal cancer；
- •Patients underwent major surgery within 4 weeks prior to neoadjuvant therapy；
- •Patients have any condition affects the absorption of capecitabine through gastrointestinal tract；
- •Patients have severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases;
- •Patients with severe concomitant diseases with estimated survival≤5 years；
- •Patients with present or previous moderate or severe liver and kidney damage；
- •Patients preparing for or previously received organ or bone marrow transplant；
- •Patients who have received immunosuppressive or systemic hormone therapy within 1 month prior to the start of neoadjuvant therapy；
- •Patients with congenital or acquired immune deficiency (such as HIV infection)；
- •Pregnant or lactating women.
Arms & Interventions
Experimental
long course radiotherapy (50 Gy/25f, 2 Gy/f, 5 days/week) for the first 5 weeks and three 21-day cycles capecitabine (1000 mg/m2, bid, po, day1-14) plus three 21-day cycles tislelizumab (200 mg, iv.gtt, day 8) for the first 9 weeks. After that, patients rested for two weeks (week 10-11)。6-8 weeks after the end of radiotherapy, patients underwent TME surgery (12-14 weeks). Thymalfasin was started on the first day of neoadjuvant chemoradiotherapy, 1.6 mg subcutaneously twice a week until the end of the last neoadjuvant treatment.
Intervention: Thymalfasin
Outcomes
Primary Outcomes
pathologic complete response
Time Frame: 1 year
All the enrolled patients will receive total mesorectal excision (TME) 7-9 weeks after the end of long course radiotherapy. The rectal specimens will be evaluated by the pathologists who are experienced on the rectal cancer diagnosis according to the 1997 Dworak grading system. The rectal cancer will be classified into 5 grades. Grade 0-3 will be considered as non-pCR while grade 4 represent pCR.
Secondary Outcomes
- neoadjuvant rectal (NAR) score(1 year)
- R0 resection rate(1 year)
- tumor regression grade（TRG）(1 year)
- anal preservation rate(1 year)
- overall survival (OS)(3 year)
- objective response rate (ORR)(1 year)
- local recurrence free survival(3 year)
- disease free survival (DFS)(3 year)