PMID- 33002819
OWN - NLM
STAT- MEDLINE
DCOM- 20201207
LR  - 20201214
IS  - 1532-1967 (Electronic)
IS  - 0305-7372 (Linking)
VI  - 90
DP  - 2020 Nov
TI  - The optimal timing for the interval to surgery after short course preoperative 
      radiotherapy (5 x5 Gy) in rectal cancer - are we too eager for surgery?
PG  - 102104
LID - S0305-7372(20)30142-0 [pii]
LID - 10.1016/j.ctrv.2020.102104 [doi]
AB  - BACKGROUND: The improved overall survival (OS) after short course preoperative 
      radiotherapy (SCPRT) using 5 x 5 Gy reported in the early rectal cancer trials 
      could not be replicated in subsequent phase III trials. This original survival 
      advantage is attributed to poor quality of surgery and the large differential in 
      local recurrence rates, with and without SCPRT. Immuno-modulation during and 
      after SCPRT and its clinical implications have been poorly investigated. We 
      propose an alternative explanation for this survival benefit in terms of 
      immunological mechanisms induced by SCPRT and the timing of surgery, which may 
      validate the concept of consolidation chemotherapy. MATERIAL AND METHODS: We 
      reviewed randomized controlled trials (RCTs) and studies of SCPRT from 1985 to 
      2019. We aimed to examine the precise timing of surgery in days following SCPRT 
      and identify evidence for immune modulation, neo-antigens and memory cell 
      induction by radiation. RESULTS: Considerable variability is reported in 
      randomised trials for median overall treatment time (OTT) from start of SCPRT to 
      surgery (8-14 days). Only three early trials showed a benefit in terms of OS from 
      SCPRT, although the level of benefit in preventing local recurrence was 
      consistent across all trials. Different patterns of immune effects are observed 
      within days after SCPRT depending on the OTT, but human leukocyte antigen (HLA)-1 
      expression was not upregulated. CONCLUSIONS: SCPRT has a substantial 
      immune-stimulatory potential. The importance of the timing of surgery after SCPRT 
      may have been underestimated. An optimal interval for surgery after 5 x 5 Gy may 
      lead to better outcomes, which is possibly exploited in total neoadjuvant therapy 
      schedules using consolidation chemotherapy. Individual patient meta-analyses from 
      appropriate SCPRT trials examining outcomes for each day and prospective trials 
      are needed to clarify the validity of this hypothesis. The interaction of SCPRT 
      with tumour adaptive immunology, in particular the kinetics and timing, should be 
      examined further.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Glynne-Jones, R
AU  - Glynne-Jones R
AD  - Radiotherapy Department, Mount Vernon Centre for Cancer Treatment, Mount Vernon 
      Hospital, Northwood HA6 2RN, United Kingdom. Electronic address: 
      rob.glynnejones@nhs.net.
FAU - Hall, M
AU  - Hall M
AD  - Department of Medical Oncology, Mount Vernon Centre for Cancer Treatment, Mount 
      Vernon Hospital, Northwood HA6 2RN, United Kingdom.
FAU - Nagtegaal, I D
AU  - Nagtegaal ID
AD  - Department of Pathology, Radboudumc, PO BOX 9101, 6500 HB Nijmegen, the 
      Netherlands.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200914
PL  - Netherlands
TA  - Cancer Treat Rev
JT  - Cancer treatment reviews
JID - 7502030
SB  - IM
MH  - Clinical Trials, Phase II as Topic
MH  - Clinical Trials, Phase III as Topic
MH  - Humans
MH  - Neoadjuvant Therapy
MH  - Randomized Controlled Trials as Topic
MH  - Rectal Neoplasms/*radiotherapy/*surgery
MH  - Time-to-Treatment
OTO - NOTNLM
OT  - 5 x 5 Gy
OT  - Immune response
OT  - Interval to surgery
OT  - Rectal adenocarcinoma
OT  - Short course preoperative radiotherapy
EDAT- 2020/10/02 06:00
MHDA- 2020/12/15 06:00
CRDT- 2020/10/01 20:19
PHST- 2020/08/04 00:00 [received]
PHST- 2020/09/04 00:00 [revised]
PHST- 2020/09/06 00:00 [accepted]
PHST- 2020/10/02 06:00 [pubmed]
PHST- 2020/12/15 06:00 [medline]
PHST- 2020/10/01 20:19 [entrez]
AID - S0305-7372(20)30142-0 [pii]
AID - 10.1016/j.ctrv.2020.102104 [doi]
PST - ppublish
SO  - Cancer Treat Rev. 2020 Nov;90:102104. doi: 10.1016/j.ctrv.2020.102104. Epub 2020 
      Sep 14.