PMID- 33374739
OWN - NLM
STAT- MEDLINE
DCOM- 20210514
LR  - 20210514
IS  - 1648-9144 (Electronic)
IS  - 1010-660X (Print)
IS  - 1010-660X (Linking)
VI  - 57
IP  - 1
DP  - 2020 Dec 23
TI  - Synergies Radiotherapy-Immunotherapy in Head and Neck Cancers. A New Concept for 
      Radiotherapy Target Volumes-"Immunological Dose Painting".
LID - 10.3390/medicina57010006 [doi]
LID - 6
AB  - The combination of immune checkpoint inhibitors and definitive radiotherapy is 
      investigated for the multimodal treatment of cisplatin non-eligible locally 
      advanced head and neck cancers (HNC). In the case of recurrent and metastatic 
      HNC, immunotherapy has shown benefit over the EXTREME protocol, being already 
      considered the standard treatment. One of the biggest challenges of multimodal 
      treatment is to establish the optimal therapy sequence so that the synergistic 
      effect is maximal. Thus, superior results were obtained for the administration of 
      anti-CTLA4 immunotherapy followed by hypofractionated radiotherapy, but the 
      anti-PD-L1 therapy demonstrates the maximum potential of radio-sensitization of 
      the tumor in case of concurrent administration. The synergistic effect of 
      radiotherapy-immunotherapy (RT-IT) has been demonstrated in clinical practice, 
      with an overall response rate of about 18% for HNC. Given the demonstrated 
      potential of radiotherapy to activate the immune system through already known 
      mechanisms, it is necessary to identify biomarkers that direct the 
      "nonresponders" of immunotherapy towards a synergistic RT-IT stimulation 
      strategy. Stimulation of the immune system by irradiation can convert 
      "nonresponder" to "responder". With the development of modern techniques, 
      re-irradiation is becoming an increasingly common option for patients who have 
      previously been treated with higher doses of radiation. In this context, 
      radiotherapy in combination with immunotherapy, both in the advanced local stage 
      and in recurrent/metastatic of HNC radiotherapy, could evolve from the "first 
      level" of knowledge (i.e., ballistic precision, dose conformity and homogeneity) 
      to "level two" of "biological dose painting" (in which the concept of tumor 
      heterogeneity and radio-resistance supports the need for doses escalation based 
      on biological criteria), and finally to the "third level" ofthe new concept of 
      "immunological dose painting". The peculiarity of this concept is that the 
      radiotherapy target volumes and tumoricidal dose can be completely reevaluated, 
      taking into account the immune-modulatory effect of irradiation. In this case, 
      the tumor target volume can include even the tumor microenvironment or a partial 
      volume of the primary tumor or metastasis, not all the gross and microscopic 
      disease. Tumoricidal biologically equivalent dose (BED) may be completely 
      different from the currently estimated values, radiotherapy treating the tumor in 
      this case indirectly by boosting the immune response. Thus, the clinical target 
      volume (CTV) can be replaced with a new immunological-clinical target volume 
      (ICTV) for patients who benefit from the RT-IT association (Image 1).
FAU - Mirestean, Camil Ciprian
AU  - Mirestean CC
AUID- ORCID: 0000-0001-6212-8008
AD  - Department of Oncology and Radiotherapy, University of Medicine and Pharmacy of 
      Craiova, 200349 Craiova, Romania.
AD  - Euroclinic Center of Oncology Iasi, 700110 Iasi, Romania.
FAU - Crisan, Anda
AU  - Crisan A
AD  - Department of Oncology and Radiotherapy, University of Medicine and Pharmacy of 
      Craiova, 200349 Craiova, Romania.
AD  - Department of Radiotherapy, County Clinical Emergency Hospital Craiova, 200642 
      Craiova, Romania.
FAU - Buzea, Calin
AU  - Buzea C
AD  - National Institute of Research and Development for Technical Physics, 700050 
      Iasi, Romania.
AD  - Department of Radiology, "Prof. Dr. Nicolae Oblu", Clinical Emergency Hospital, 
      700309 Iasi, Romania.
FAU - Iancu, Roxana Irina
AU  - Iancu RI
AD  - Department of Oral Pathology, "Gr. T. Popa" University of Medicine and Pharmacy, 
      700115 Iasi, Romania.
AD  - Department of Oncology and Radiotherapy, "Gr. T. Popa" University of Medicine and 
      Pharmacy, 700115 Iasi, Romania.
AD  - Department of Clinical Laboratory, "St. Spiridon" Emergency Hospital, 700111 
      Iasi, Romania.
FAU - Iancu, DragosPetru Teodor
AU  - Iancu DT
AD  - Department of Oral Pathology, "Gr. T. Popa" University of Medicine and Pharmacy, 
      700115 Iasi, Romania.
AD  - Department of Oncology and Radiotherapy, "Gr. T. Popa" University of Medicine and 
      Pharmacy, 700115 Iasi, Romania.
AD  - Department of Radiotherapy, Regional Institute of Oncology, 700483 Iasi, Romania.
LA  - eng
PT  - Journal Article
DEP - 20201223
PL  - Switzerland
TA  - Medicina (Kaunas)
JT  - Medicina (Kaunas, Lithuania)
JID - 9425208
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Cisplatin
MH  - *Head and Neck Neoplasms/radiotherapy
MH  - Humans
MH  - Immunotherapy
MH  - *Re-Irradiation
MH  - Tumor Burden
MH  - Tumor Microenvironment
PMC - PMC7824056
OTO - NOTNLM
OT  - ab-scopal
OT  - head and neck cancers
OT  - immunotherapy
OT  - radiotherapy
OT  - re-irradiation
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/31 06:00
MHDA- 2021/05/15 06:00
PMCR- 2020/12/23
CRDT- 2020/12/30 01:02
PHST- 2020/11/24 00:00 [received]
PHST- 2020/12/16 00:00 [revised]
PHST- 2020/12/21 00:00 [accepted]
PHST- 2020/12/30 01:02 [entrez]
PHST- 2020/12/31 06:00 [pubmed]
PHST- 2021/05/15 06:00 [medline]
PHST- 2020/12/23 00:00 [pmc-release]
AID - medicina57010006 [pii]
AID - medicina-57-00006 [pii]
AID - 10.3390/medicina57010006 [doi]
PST - epublish
SO  - Medicina (Kaunas). 2020 Dec 23;57(1):6. doi: 10.3390/medicina57010006.