PMID- 37217353
OWN - NLM
STAT- MEDLINE
DCOM- 20230531
LR  - 20230531
IS  - 1671-0274 (Print)
IS  - 1671-0274 (Linking)
VI  - 26
IP  - 5
DP  - 2023 May 25
TI  - [Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total 
      neoadjuvant therapy of locally advanced rectal cancer: the preliminary 
      single-center findings of a prospective, multicentre, randomized phase II trial 
      (TORCH)].
PG  - 448-458
LID - 10.3760/cma.j.cn441530-20230107-00010 [doi]
AB  - Objective: Total neoadjuvant therapy has been used to improve tumor responses and 
      prevent distant metastases in patients with locally advanced rectal cancer 
      (LARC). Patients with complete clinical responses (cCR) then have the option of 
      choosing a watch and wait (W&W) strategy and organ preservation. It has recently 
      been shown that hypofractionated radiotherapy has better synergistic effects with 
      PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, 
      increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to 
      immunotherapy. Thus, in this trial we aimed to determine whether total 
      neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a 
      PD-1 inhibitor improves the degree of tumor regression in patients with LARC. 
      Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH 
      Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus 
      </=10 cm) are eligible and are randomly assigned to consolidation or induction 
      arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six 
      cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the 
      induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by 
      four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal 
      excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary 
      endpoint is the complete response rate (CR, pathological complete response [pCR] 
      plus continuous cCR for more than 1 year). The secondary endpoints include rates 
      of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 
      62 patients attending our center were enrolled (Consolidation arm: 34, Induction 
      arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR 
      type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) 
      had Stage III disease. The following important characteristics were distributed 
      as follows: lower location (</=5 cm from anus, 48/62, 77.4%), deeper invasion by 
      primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and 
      high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 
      patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) 
      completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 
      29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 
      patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 
      TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these 
      patients was found to have pCR after surgery whereas the other two adopted a W&W 
      strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), 
      respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic 
      AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 
      78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. 
      The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia 
      (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase 
      (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), 
      with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs 
      were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with 
      toripalimab can achieve a surprisingly good CR rate in patients with LARC and 
      thus has the potential to offer new treatment options for organ preservation in 
      patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary 
      findings of a single center show good tolerability, the main Grade III-IV AE 
      being thrombocytopenia. The significant efficacy and long-term prognostic benefit 
      need to be determined by further follow-up.
FAU - Wang, Y Q
AU  - Wang YQ
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
FAU - Shen, L J
AU  - Shen LJ
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
FAU - Wan, J F
AU  - Wan JF
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
FAU - Zhang, H
AU  - Zhang H
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
FAU - Wang, Y
AU  - Wang Y
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
FAU - Wu, X
AU  - Wu X
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
FAU - Wang, J W
AU  - Wang JW
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
FAU - Wang, R J
AU  - Wang RJ
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Colorectal Surgery, Fudan University Shanghai Cancer 
      Center, Shanghai 200032, China.
FAU - Sun, Y Q
AU  - Sun YQ
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Radiology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China.
FAU - Tong, T
AU  - Tong T
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Radiology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China.
FAU - Huang, D
AU  - Huang D
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Pathology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China.
FAU - Wang, L
AU  - Wang L
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Pathology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China.
FAU - Sheng, W Q
AU  - Sheng WQ
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Pathology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China.
FAU - Zhang, X
AU  - Zhang X
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Ultrasound, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China.
FAU - Cai, G X
AU  - Cai GX
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Colorectal Surgery, Fudan University Shanghai Cancer 
      Center, Shanghai 200032, China.
FAU - Xu, Y
AU  - Xu Y
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Colorectal Surgery, Fudan University Shanghai Cancer 
      Center, Shanghai 200032, China.
FAU - Cai, S J
AU  - Cai SJ
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 
      200032, China Department of Colorectal Surgery, Fudan University Shanghai Cancer 
      Center, Shanghai 200032, China.
FAU - Zhang, Z
AU  - Zhang Z
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
FAU - Xia, F
AU  - Xia F
AD  - Department of Radiation Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai 200032, China Department of Oncology, Shanghai Medical College, Fudan 
      University, Shanghai 200032, China Shanghai Key Laboratory of Radiation Oncology, 
      Shanghai 200032, China Shanghai Clinical Research Center for Radiation Oncology, 
      Shanghai 200032, China.
LA  - chi
GR  - 82003229/National Natural Science Foundation of China/
PT  - Clinical Trial, Phase II
PT  - English Abstract
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - China
TA  - Zhonghua Wei Chang Wai Ke Za Zhi
JT  - Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery
JID - 101177990
RN  - 0 (Immune Checkpoint Inhibitors)
SB  - IM
MH  - Humans
MH  - Middle Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
MH  - Chemoradiotherapy
MH  - Immune Checkpoint Inhibitors/therapeutic use
MH  - Neoadjuvant Therapy
MH  - Prospective Studies
MH  - *Rectal Neoplasms/pathology
MH  - *Thrombocytopenia/drug therapy
MH  - Treatment Outcome
MH  - Adult
MH  - Aged
EDAT- 2023/05/23 01:06
MHDA- 2023/05/24 06:42
CRDT- 2023/05/22 21:54
PHST- 2023/05/24 06:42 [medline]
PHST- 2023/05/23 01:06 [pubmed]
PHST- 2023/05/22 21:54 [entrez]
AID - 10.3760/cma.j.cn441530-20230107-00010 [doi]
PST - ppublish
SO  - Zhonghua Wei Chang Wai Ke Za Zhi. 2023 May 25;26(5):448-458. doi: 
      10.3760/cma.j.cn441530-20230107-00010.